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Zhang Q, Hao X, Sun X, Jia YC, Zhu YY, Yang YX, Zhu BT. 4-Hydroxyestrogen metabolites strongly prevent chemically-induced ferroptotic hepatocyte injury in vitro and in vivo. Eur J Pharmacol 2025; 993:177313. [PMID: 39921062 DOI: 10.1016/j.ejphar.2025.177313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/10/2025]
Abstract
Ferroptosis is a regulated cell death characterized by excessive accumulation of toxic lipid reactive oxygen species (ROS). Ferroptosis is an underlying cause in some human diseases, including the drug-induced liver injury. The present study aims to determine whether 4-hydroxyestrone (4-OH-E1) and 4-hydroxyestradiol (4-OH-E2), two endogenous catechol estrogens, can prevent chemically-induced ferroptotic hepatocyte injury in vitro and in vivo. The induction of ferroptotic cell death by erastin and RSL3 in rat H-4-II-E and human HuH-7 hepatoma cells is used as in vitro models. 4-OH-E1 and 4-OH-E2 each exhibit a strong protection against erastin/RSL3-induced ferroptosis in H-4-II-E hepatoma cells, and they also strongly abrogate erastin/RSL3-induced accumulation of cellular NO, ROS and lipid-ROS. A similar protective effect is observed with 4-OH-E1 and 4-OH-E2 in RSL3-induced ferroptosis in HuH-7 cells. Mechanistically, these two catechol estrogens protect hepatoma cells against chemically-induced ferroptosis mainly through binding to cellular PDI protein with a high affinity, which leads to inhibition of PDI-catalyzed NOS dimerization (activation), thereby preventing the accumulation of cellular NO, ROS and lipid-ROS. In addition, the direct antioxidant activity of these two estrogens may also partially contribute to their cytoprotective effect. In vivo animal studies show that 4-OH-E1 and 4-OH-E2 also have a strong protective effect against acetaminophen-induced liver injury in a mouse model. Together, the results of this study demonstrate that 4-OH-E1 and 4-OH-E2 are endogenous factors with a strong protective activity against chemically-induced hepatocyte injury both in vitro and in vivo.
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Affiliation(s)
- Qi Zhang
- Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, China
| | - Xiangyu Hao
- Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, China
| | - Xi Sun
- Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, China
| | - Yi-Chen Jia
- Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, China
| | - Yan-Yin Zhu
- Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, China
| | - Yong Xiao Yang
- Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, China
| | - Bao Ting Zhu
- Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, China; Shenzhen Bay Laboratory, Shenzhen, 518172, China.
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Huang X, Hou MJ, Zhu BT. Protection of HT22 neuronal cells against chemically-induced ferroptosis by catechol estrogens: protein disulfide isomerase as a mechanistic target. Sci Rep 2024; 14:23988. [PMID: 39402104 PMCID: PMC11473836 DOI: 10.1038/s41598-024-74742-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 09/30/2024] [Indexed: 10/17/2024] Open
Abstract
Ferroptosis is a form of regulated cell death, characterized by excessive iron-dependent lipid peroxidation. Biochemically, ferroptosis can be selectively induced by erastin through glutathione depletion or through inhibition of glutathione peroxidase 4 by RSL3, which leads to accumulation of cytotoxic lipid reactive oxygen species (ROS). Protein disulfide isomerase (PDI) was recently shown to mediate erastin/RSL3-induced ferroptosis and thus also become a new target for protection against chemically-induced ferroptosis. The present study aims to identify endogenous compounds that can protect against erastin/RSL3-induced ferroptotic cell death. We find that 2-hydroxyestrone, 2-hydroxyestradiol, 4-hydroxyestrone and 4-hydroxyestradiol, four major endogenous catechol estrogens, are effective inhibitors of PDI, and can strongly protect against chemically-induced ferroptotic cell death in cultured HT22 mouse hippocampal neuronal cells. The CETSA assay showed that these catechol estrogens can bind to PDI in live cells. PDI knockdown attenuates the protective effect of these catechol estrogens against chemically-induced ferroptosis. Mechanistically, inhibition of PDI's catalytic activity by catechol estrogens abrogates erastin/RSL3-induced dimerization of nitric oxide synthase, thereby preventing the subsequent accumulation of cellular nitric oxide, ROS and lipid-ROS, and ultimately ferroptotic cell death. In addition, joint treatment of cells with catechol estrogens also abrogates erastin/RSL3-induced upregulation of nitric oxide synthase protein levels, which also contributes to the cytoprotective effect of the catechol estrogens. In conclusion, the present study demonstrates that the catechol estrogens are protectors of HT22 neuronal cells against chemically-induced ferroptosis, and inhibition of PDI's catalytic activity by these estrogens contributes to a novel, estrogen receptor-independent mechanism of cytoprotection.
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Affiliation(s)
- Xuanqi Huang
- Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Road, Longgang District, Shenzhen, 518172, China
| | - Ming-Jie Hou
- Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Road, Longgang District, Shenzhen, 518172, China
| | - Bao Ting Zhu
- Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Road, Longgang District, Shenzhen, 518172, China.
- Shenzhen Bay Laboratory, Shenzhen, 518055, China.
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Shi Y, Ma J, Li S, Liu C, Liu Y, Chen J, Liu N, Liu S, Huang H. Sex difference in human diseases: mechanistic insights and clinical implications. Signal Transduct Target Ther 2024; 9:238. [PMID: 39256355 PMCID: PMC11387494 DOI: 10.1038/s41392-024-01929-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 06/26/2024] [Accepted: 07/23/2024] [Indexed: 09/12/2024] Open
Abstract
Sex characteristics exhibit significant disparities in various human diseases, including prevalent cardiovascular diseases, cancers, metabolic disorders, autoimmune diseases, and neurodegenerative diseases. Risk profiles and pathological manifestations of these diseases exhibit notable variations between sexes. The underlying reasons for these sex disparities encompass multifactorial elements, such as physiology, genetics, and environment. Recent studies have shown that human body systems demonstrate sex-specific gene expression during critical developmental stages and gene editing processes. These genes, differentially expressed based on different sex, may be regulated by androgen or estrogen-responsive elements, thereby influencing the incidence and presentation of cardiovascular, oncological, metabolic, immune, and neurological diseases across sexes. However, despite the existence of sex differences in patients with human diseases, treatment guidelines predominantly rely on male data due to the underrepresentation of women in clinical trials. At present, there exists a substantial knowledge gap concerning sex-specific mechanisms and clinical treatments for diverse diseases. Therefore, this review aims to elucidate the advances of sex differences on human diseases by examining epidemiological factors, pathogenesis, and innovative progress of clinical treatments in accordance with the distinctive risk characteristics of each disease and provide a new theoretical and practical basis for further optimizing individualized treatment and improving patient prognosis.
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Affiliation(s)
- Yuncong Shi
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
| | - Jianshuai Ma
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
| | - Sijin Li
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
| | - Chao Liu
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
| | - Yuning Liu
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
| | - Jie Chen
- Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ningning Liu
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Shiming Liu
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
| | - Hui Huang
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China.
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
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Allegra A, Caserta S, Genovese S, Pioggia G, Gangemi S. Gender Differences in Oxidative Stress in Relation to Cancer Susceptibility and Survival. Antioxidants (Basel) 2023; 12:1255. [PMID: 37371985 DOI: 10.3390/antiox12061255] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 06/08/2023] [Accepted: 06/10/2023] [Indexed: 06/29/2023] Open
Abstract
Genetic, developmental, biochemical, and environmental variables interact intricately to produce sex differences. The significance of sex differences in cancer susceptibility is being clarified by numerous studies. Epidemiological research and cancer registries have revealed over the past few years that there are definite sex variations in cancer incidence, progression, and survival. However, oxidative stress and mitochondrial dysfunction also have a significant impact on the response to treatment of neoplastic diseases. Young women may be more protected from cancer than men because most of the proteins implicated in the regulation of redox state and mitochondrial function are under the control of sexual hormones. In this review, we describe how sexual hormones control the activity of antioxidant enzymes and mitochondria, as well as how they affect several neoplastic diseases. The molecular pathways that underlie the gender-related discrepancies in cancer that have been identified may be better understood, which may lead to more effective precision medicine and vital information on treatment options for both males and females with neoplastic illnesses.
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Affiliation(s)
- Alessandro Allegra
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood 'Gaetano Barresi', University of Messina, 98125 Messina, Italy
| | - Santino Caserta
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood 'Gaetano Barresi', University of Messina, 98125 Messina, Italy
| | - Sara Genovese
- Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98164 Messina, Italy
| | - Giovanni Pioggia
- Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98164 Messina, Italy
| | - Sebastiano Gangemi
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
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Matsuda T, Ogata H, Kanno M, Ishikawa A, Yamada M, Sakamaki-Sunaga M. Effects of the menstrual cycle on oxidative stress and antioxidant response to high-intensity intermittent exercise until exhaustion in healthy women. J Sports Med Phys Fitness 2020; 60:1335-1341. [PMID: 32550716 DOI: 10.23736/s0022-4707.20.10868-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND This study aimed to investigate the effects of the menstrual cycle on the oxidative stress and antioxidant response during high-intensity intermittent exercise until exhaustion in healthy women who habitually exercised. METHODS Ten women with normal menstrual cycle completed 2 menstrual cycle phases, including the early follicular phase (FP) and the midluteal phase (LP). High-intensity exercise until exhaustion was performed on each test day. Blood samples were collected before the exercise (Pre), immediately after the exercise (Post0), and 60 minutes after the exercise (Post60). The levels of estradiol; progesterone; oxidative stress, which was measured as diacron reactive oxygen metabolites (d-ROMs); and antioxidant capacity, which was measured as the biological antioxidant potential (BAP), were assessed. RESULTS The levels of serum estradiol and progesterone at Pre were significantly higher in the LP than in the FP (P<0.01). There were no significant differences in the d-ROMs, BAP, and BAP/d-ROMs between the FP and the LP at Pre, Post0, and Post60. Compared with the FP, the LP had significantly lower d-ROMs change rate from Pre at Post0 and Post60 (P<0.05). Moreover, the BAP/d-ROMs change rate from Pre showed a significantly higher trend in the LP than in the FP at Post0 and Post60 (P=0.06). CONCLUSIONS In women with regular menstrual cycle, oxidative stress during exercise and recovery may be eliminated during the LP, when the estradiol and progesterone levels are higher, compared with those during the FP.
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Affiliation(s)
- Tomoka Matsuda
- Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan -
| | - Hazuki Ogata
- Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan
| | - Moe Kanno
- Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan
| | - Akira Ishikawa
- Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan
| | - Mizuki Yamada
- Department of Exercise Physiology, Nippon Sport Science University, Tokyo, Japan
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Kandemir B, Ates S, Kurutas EB, Durduran Y, Erayman I, Bitirgen M. GPER-1 in chronic hepatitis B. JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES 2020. [DOI: 10.1080/16878507.2020.1762527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
- Bahar Kandemir
- Department of Infectious Diseases and Clinical Microbiology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Selma Ates
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey
| | - Ergül Belge Kurutas
- Department of Biochemistry, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey
| | - Yasemin Durduran
- Department of Public Health, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Ibrahim Erayman
- Department of Infectious Diseases and Clinical Microbiology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Mehmet Bitirgen
- Department of Infectious Diseases and Clinical Microbiology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
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7
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Delhez A, Lefebvre P, Péqueux C, Malgrange B, Delacroix L. Auditory function and dysfunction: estrogen makes a difference. Cell Mol Life Sci 2020; 77:619-635. [PMID: 31522250 PMCID: PMC11105012 DOI: 10.1007/s00018-019-03295-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 08/30/2019] [Accepted: 09/05/2019] [Indexed: 01/09/2023]
Abstract
Estrogen is the major female hormone involved in reproductive functions, but it also exerts a variety of additional roles in non-reproductive organs. In this review, we highlight the preclinical and clinical studies that have pointed out sex differences and estrogenic influence on audition. We also describe the experimental evidences supporting a protective role of estrogen towards acquired forms of hearing loss. Although a high level of endogenous estrogen is associated with a better hearing function, hormonal treatments at menopause have provided contradictory outcomes. The various factors that are likely to explain these discrepancies include the treatment regimen as well as the hormonal status and responsiveness of the patients. The complexity of estrogen signaling is being untangled and many downstream effectors of its genomic and non-genomic actions have been identified in other systems. Based on these advances and on the common physio-pathological events that underlie age-related, drug or noise-induced hearing loss, we discuss potential mechanisms for their protective actions in the cochlea.
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Affiliation(s)
- Amandine Delhez
- GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liege, Liege, Belgium
- Department of ENT, CHU de Liege, Liege, Belgium
| | | | - Christel Péqueux
- GIGA-Cancer, Laboratory of Tumors Biology and Development, University of Liege, Liege, Belgium
| | - Brigitte Malgrange
- GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liege, Liege, Belgium
| | - Laurence Delacroix
- GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liege, Liege, Belgium.
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8
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Manivannan C, Baskaran S, Vijayakumar P, Renganathan R. Spectroscopic investigation and computational studies on the interaction of Acriflavine with various estrogens. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2019; 206:622-629. [PMID: 30056036 DOI: 10.1016/j.saa.2018.07.047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 06/23/2018] [Accepted: 07/15/2018] [Indexed: 06/08/2023]
Abstract
The fluorescence quenching of Acriflavine (AFN) by certain estrogens was examined in aqueous media by employing steady state and time-resolved fluorescence measurements. The absorption spectra of AFN change with significant bathochromic shift in presence of quencher molecules. The quenching behavior was examined by correlating the bimolecular quenching rate constant (kq) with the free energy change (ΔG). The decrease in quenching rate constant depends on the increase in oxidation potential of quencher molecules. The fluorescence quenching experiments were carried out in different solvents of varying polarities and reveals the possibility of charge transfer quenching mechanism. Lifetime measurements indicate static quenching. The quenching behavior is addressed from bond dissociation enthalpy (BDE) calculations. The antioxidant activity of estrogen compounds were evaluated by deoxyribose oxidation assay.
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Affiliation(s)
- C Manivannan
- Department of Chemistry, Bannari Amman Institute of Technology, Sathyamangalam-01, India.
| | - S Baskaran
- Department of Chemistry, Tsinghua University, Beijing 100084, PR China
| | - P Vijayakumar
- School of Chemistry, Bharathidasan University, Tiruchirappalli-24, India
| | - R Renganathan
- School of Chemistry, Bharathidasan University, Tiruchirappalli-24, India
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9
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Kafami M, Hosseini M, Niazmand S, Farrokhi E, Hajzadeh MAR, Nazemi S. The effects of estradiol and testosterone on renal tissues oxidative after central injection of angiotensin II in female doca - salt treated rats. Horm Mol Biol Clin Investig 2018; 37:/j/hmbci.ahead-of-print/hmbci-2018-0044/hmbci-2018-0044.xml. [PMID: 30398970 DOI: 10.1515/hmbci-2018-0044] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 09/11/2018] [Indexed: 02/03/2023]
Abstract
Background Although numerous studies have proven that estrogen (Est) has a protective effect on the development of hypertension, more research needs to be done to show its detailed mechanism in a variety of hypertension. The important role of active oxygen species in blood pressure is well defined. We examined whether or not sex hormones change the growth of reactive oxygen species (ROS) in kidneys after central microinjection of angiotensin II (Ang II). Materials and methods Female Wistar rats, 8 weeks old (200 ± 10 g) were used in this study. The animal groups were (1) Sham, (2) Ovariectomy (OVX), (3) Sham-Hypertension (Sham-Hyper), (4) OVX-Hypertension (OVX-Hyper), (5) Sham-Hyper-Est, (6) OVX-Hyper-Est; (7) Sham-Hyper-Testosterone (Tst) and (8) OVX-Hyper-Tst. Solutions of 1% NaCl and 0.1 KCl were used and desoxycorticostrone (doca-salt) was injected (45 mg/kg) 3 times a week in Hypertension groups. Estradiol and Tst (2 mg/kg and 5 mg/kg; daily; subcutaneously) for 4 weeks. Ang II (50 μM, 5 μL) was microinjected by intracerebroventricular ( i.c.v.) infusion and malondialdehyde (MDA) and thiol in the kidneys were measured. Results MDA in the kidneys was increased by Ang II and doca-salt treatments. Both estradiol and Tst decreased the kidney's MDA. The level of thiol was higher in Hyper groups and reversed after treatment with estradiol and Tst. Conclusions Our findings suggest that central effect of Ang II on blood pressure and kidney disease is accompanied with increased levels of oxidative stress in the kidneys. Indeed sex hormones change the ROS level in the kidneys after central microinjection of Ang II..
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Affiliation(s)
- Marzieh Kafami
- Cellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar Universityof Medical Sciences, Sabzevar, Iran, Phone: 0098-051-4446070, Fax: 0098-051-4445648
| | - Mahmoud Hosseini
- Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saeed Niazmand
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Esmaeil Farrokhi
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mosa Al-Reza Hajzadeh
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Samad Nazemi
- Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
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Comparison of the antioxidant effects of equine estrogens, red wine components, vitamin E, and probucol on low-density lipoprotein oxidation in postmenopausal women. Menopause 2018; 25:1214-1223. [DOI: 10.1097/gme.0000000000001222] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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MRAZKOVA H, LISCHKE R, HERGET J. Influence of Gender on Ischemia-Reperfusion Injury in Lungs in an Animal Model. Physiol Res 2016; 65:953-958. [DOI: 10.33549/physiolres.933273] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
As with other organ transplants even lung transplantation raises the question of the possibility of the influence of gender on ischemia-reperfusion injury. This is a current topic especially for increasingly utilized method of lung transplantation from non-heart-beating donors, where reperfusion preceded by a period of warm and cold ischemia with subsequent treatment options for lung graft reperfusion. For measurements we used our laboratory previously created and validated animal model for ex vivo lung transplantation. As with other organ systems of our monitoring resulted protective effect of female sex on ischemia reperfusion lung injury. In two of the three parameters that were monitored, we found a significant difference. In females, higher oxygen transfer ability after reperfusion was manifested as well as lower perfusion pressure (vascular compliance). Conversely, weight gain (the development of pulmonary edema) in males was not significant difference from the females. These conclusions could cause further studies leading to influence the selection of appropriate donor grafts.
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Affiliation(s)
- H. MRAZKOVA
- Third Department of Surgery, University Hospital Motol and First Medical School, Charles University in Prague, Prague, Czech Republic
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12
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Qian M, Engler-Chiurazzi EB, Lewis SE, Rath NP, Simpkins JW, Covey DF. Structure-activity studies of non-steroid analogues structurally-related to neuroprotective estrogens. Org Biomol Chem 2016; 14:9790-9805. [PMID: 27714297 PMCID: PMC5525543 DOI: 10.1039/c6ob01726f] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Estrone and 17β-estradiol are phenolic steroids that are known to be neuroprotective in multiple models of neuronal injury. Previous studies have identified the importance of their phenolic steroid A-ring for neuroprotection and have identified ortho substituents at the C-2 and C-4 positions on the phenol ring that enhance this activity. To investigate the importance of the steroid ring system for neuroprotective activity, phenolic compounds having the cyclopent[b]anthracene, cyclopenta[b]phenanthrene, benz[f]indene, benz[e]indene, indenes linked to a phenol, and a phenolic spiro ring system were prepared. New synthetic methods were developed to make some of the cyclopent[b]anthracene analogues as well as the spiro ring system. Compounds were evaluated for their ability to protect HT-22 hippocampal neurons from glutamate neurotoxicity and their activity relative to a potent neuroprotective analogue of 17β-estradiol was determined. An adamantyl substituent placed ortho to the phenolic hydroxyl group gave neuroprotective analogues in all ring systems studied.
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Affiliation(s)
- Mingxing Qian
- Department of Developmental Biology, Campus Box 8103, Washington University in St. Louis, School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
| | | | - Sara E Lewis
- Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, WV 26506, USA
| | - Nigam P Rath
- Department of Chemistry and Biochemistry and Center for Nanoscience, University of Missouri-St. Louis, St. Louis, MO 63121, USA
| | - James W Simpkins
- Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, WV 26506, USA
| | - Douglas F Covey
- Department of Developmental Biology, Campus Box 8103, Washington University in St. Louis, School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA. and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA and Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
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13
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Kodrík D, Bednářová A, Zemanová M, Krishnan N. Hormonal Regulation of Response to Oxidative Stress in Insects-An Update. Int J Mol Sci 2015; 16:25788-816. [PMID: 26516847 PMCID: PMC4632827 DOI: 10.3390/ijms161025788] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 10/07/2015] [Accepted: 10/15/2015] [Indexed: 12/20/2022] Open
Abstract
Insects, like other organisms, must deal with a wide variety of potentially challenging environmental factors during the course of their life. An important example of such a challenge is the phenomenon of oxidative stress. This review summarizes the current knowledge on the role of adipokinetic hormones (AKH) as principal stress responsive hormones in insects involved in activation of anti-oxidative stress response pathways. Emphasis is placed on an analysis of oxidative stress experimentally induced by various stressors and monitored by suitable biomarkers, and on detailed characterization of AKH’s role in the anti-stress reactions. These reactions are characterized by a significant increase of AKH levels in the insect body, and by effective reversal of the markers—disturbed by the stressors—after co-application of the stressor with AKH. A plausible mechanism of AKH action in the anti-oxidative stress response is discussed as well: this probably involves simultaneous employment of both protein kinase C and cyclic adenosine 3′,5′-monophosphate pathways in the presence of extra and intra-cellular Ca2+ stores, with the possible involvement of the FoxO transcription factors. The role of other insect hormones in the anti-oxidative defense reactions is also discussed.
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Affiliation(s)
- Dalibor Kodrík
- Institute of Entomology, Biology Centre, Academy of Sciences, Branišovská 31, 370 05 České Budějovice, Czech Republic.
- Faculty of Science, University of South Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic.
| | - Andrea Bednářová
- Institute of Entomology, Biology Centre, Academy of Sciences, Branišovská 31, 370 05 České Budějovice, Czech Republic.
- Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA.
| | - Milada Zemanová
- Institute of Entomology, Biology Centre, Academy of Sciences, Branišovská 31, 370 05 České Budějovice, Czech Republic.
- Faculty of Science, University of South Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic.
| | - Natraj Krishnan
- Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA.
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Cengiz M, Ozenirler S, Yılmaz G. Estrogen receptor alpha expression and liver fibrosis in chronic hepatitis C virus genotype 1b: a clinicopathological study. HEPATITIS MONTHLY 2014; 14:e21885. [PMID: 25368658 PMCID: PMC4214133 DOI: 10.5812/hepatmon.21885] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 09/06/2014] [Accepted: 09/07/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatic damage due to chronic hepatitis C virus (HCV) genotype 1b infection varies widely. OBJECTIVES We aimed to investigate whether estrogen receptor alpha (ERα) plays a role in liver fibrosis in patients infected with HCV genotype 1b. PATIENTS AND METHODS All the consecutive patients who received the same standard treatment protocol for HCV genotype 1b were subdivided into two subgroups according to their fibrosis scores as fibrotic stages < 2 in mild fibrosis group and fibrotic stages ≥ 2 in advanced fibrosis group, depending on the presence of septal fibrosis. ERα was stained in liver biopsy specimens. Demographics and clinical properties were compared between the groups. Multivariate logistic regression analysis was performed to predict advanced fibrosis. RESULTS There were 66 patients in the mild fibrosis group and 24 in the advanced fibrosis group. Among the mild and advanced fibrosis groups, 65.1% and 50%were female, respectively (P = 0.19). There was an inverse correlation between ERα and fibrotic stage (r: -0.413; P < 0.001). Age, platelet counts, neutrophil counts, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transferase (GGT) and ERα were statistically significant in the univariate analysis. In multivariate logistic regression analyses, ERα expression continued to be an independent predicting factor of liver fibrosis in patients infected with chronic HCV genotype 1b (OR: 0.10; 95% CI: 0.018-0.586; P < 0.001). CONCLUSIONS ERα expression in liver was inversely correlated with liver fibrosis among patients infected with chronic HCV genotype 1b.
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Affiliation(s)
- Mustafa Cengiz
- Department of Gastroenterology, Dr. A.Y. Ankara Oncology Training and Research Hospital, Ankara, Turkey
- Corresponding Author: Mustafa Cengiz, Department of Gastroenterology, Dr. A.Y. Ankara Oncology Training and Research Hospital, Ankara, Turkey. Tel: +90-3123360909, Fax: +90-31233403 52, E-mail:
| | - Seren Ozenirler
- Department of Gastroenterology, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Guldal Yılmaz
- Deparment of Pathology, Faculty of Medicine, Gazi University, Ankara, Turkey
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Andriichuk A, Tkachenko H, Kurhaluk N. Gender Differences of Oxidative Stress Biomarkers and Erythrocyte Damage in Well-Trained Horses During Exercise. J Equine Vet Sci 2014. [DOI: 10.1016/j.jevs.2014.05.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Pourganji M, Hosseini M, Soukhtanloo M, Zabihi H, Hadjzadeh MAR. Protective role of endogenous ovarian hormones against learning and memory impairments and brain tissues oxidative damage induced by lipopolysaccharide. IRANIAN RED CRESCENT MEDICAL JOURNAL 2014; 16:e13954. [PMID: 24829769 PMCID: PMC4005431 DOI: 10.5812/ircmj.13954] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2013] [Revised: 12/05/2013] [Accepted: 12/16/2013] [Indexed: 01/03/2023]
Abstract
BACKGROUND The contribution of neuroinflammation in Alzheimer's disease (AD) has been widely reported. The effects of female gonadal hormones in both neuroinflammation and brain cognitive functions have also been well considered. OBJECTIVES In the present study, the possible protective role for endogenous ovarian hormones against learning and memory impairment as well as brain tissues oxidative damage induced by lipopolysachride (LPS) was investigated in rats. MATERIALS AND METHODS THE RATS WERE DIVIDED INTO FOUR GROUPS: Sham-LPS, Ovariectomized (OVX)-LPS, Sham, and OVX. The animals of sham group were in proestrous phase in which the serum concentration of estradiol is high. The Sham-LPS and OVX-LPS groups were treated with LPS (250 µg/kg) before acquisition. The animals were examined using passive avoidance (PA) test. The brains were then removed and malondialdehyde (MDA) and total thiol groups concentrations were measured. RESULTS The time latency to enter the dark compartment by OVX-LPS group was shorter than that of OVX at both first and 24th hours after the shock (P < 0.05 - P < 0.001). In Sham-LPS and OVX-LPS groups, total thiol concentration in hippocampal and cortical tissues were significantly lower while MDA concentrations were higher than that of Sham and OVX groups (P < 0.05 - P < 0.001). ). The hippocampal MDA concentration in OVX-LPS group was higher than Sham- LPS group (P < 0.01). CONCLUSIONS Brain tissue oxidative damage contributed in deleterious effects of LPS on learning and memory. Some protective effects for the endogenous ovarian hormones against damaging effects of LPS on learning and memory function, as well as brain tissues oxidative damage could be postulated; however, it needs more investigation.
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Affiliation(s)
- Masoume Pourganji
- Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Mahmoud Hosseini
- Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
- Corresponding Author: Mahmoud Hosseini, Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran. Tel: +98-05118828565, Fax: +98-05118828564, E-mail:
| | - Mohammad Soukhtanloo
- Department of Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Hoda Zabihi
- Department of Biology, Faculty of Biological Sciences, Kharazmi University of Tehran, Tehran, IR Iran
| | - Mosa Al-reza Hadjzadeh
- Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
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Liu SH, Lazo M, Koteish A, Linda Kao WH, Shih MH, Bonekamp S, Hernaez R, Clark JM. Oral contraceptive pill use is associated with reduced odds of nonalcoholic fatty liver disease in menstruating women: results from NHANES III. J Gastroenterol 2013; 48:1151-9. [PMID: 23188092 PMCID: PMC4170913 DOI: 10.1007/s00535-012-0715-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2012] [Accepted: 11/05/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND Higher prevalence of nonalcoholic fatty liver disease (NAFLD) in men and postmenopausal women than in premenopausal women has suggested a potential role of sex hormones in the pathogenesis of the disease. We sought to evaluate the association between oral contraceptive pills (OCP) and NAFLD and to determine whether adiposity mediates any effect. METHODS We included 4338 women aged 20-60 years who were enrolled in the Third National Health and Nutrition Examination Survey from 1988 to 1994 in a population-based cross-sectional study. We defined NAFLD as moderate-severe steatosis on ultrasonography in women without excessive alcohol use or other identifiable causes. OCP use was based on self-report and was categorized as never, former or current use. RESULTS The overall weighted prevalence of NAFLD was 11.6 % but lower in current (6.7 %) than in former (12.0 %) or never users (15.6 %, P = 0.016). In the multivariable model, current OCP users experienced a 50 % lower odds of NAFLD than never users (adjusted odds ratio 0.50; 95 % confidence interval 0.26, 0.98) after adjusting for age, race/ethnicity, smoking status, history of diabetes or hypertension and education. Further adjustment for body mass index or waist circumference significantly attenuated the OCP-NAFLD relationship. CONCLUSIONS In this large US-representative population, OCP use was associated with reduced odds of NAFLD. However, this association could be mediated or confounded by adiposity. Prospective studies are needed to further clarify the causal role of sex hormone.
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Affiliation(s)
- Su-Hsun Liu
- Department of Epidemiology, Johns Hopkins Bloomberg, School of Public Health, 2024 E. Monument St., Suite 2-600, Baltimore, MD 21287, USA
| | - Mariana Lazo
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument St., Suite 2-600, Baltimore, MD 21287, USA
| | - Ayman Koteish
- Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
| | - W. H. Linda Kao
- Department of Epidemiology, Johns Hopkins Bloomberg, School of Public Health, 2024 E. Monument St., Suite 2-600, Baltimore, MD 21287, USA
| | - Ming-Hsiung Shih
- Department of Family Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Susanne Bonekamp
- Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
| | - Ruben Hernaez
- Department of Epidemiology, Johns Hopkins Bloomberg, School of Public Health, 2024 E. Monument St., Suite 2-600, Baltimore, MD 21287, USA. Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. Department of Medicine, Washington Hospital Center/Georgetown University Hospital, Washington, DC, USA
| | - Jeanne M. Clark
- Department of Epidemiology, Johns Hopkins Bloomberg, School of Public Health, 2024 E. Monument St., Suite 2-600, Baltimore, MD 21287, USA. Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
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[Non-alcoholic fatty liver disease in obese children and adolescents]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2013; 56:517-27. [PMID: 23529597 DOI: 10.1007/s00103-012-1639-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and adolescents in industrialized countries. Recent studies have demonstrated a prevalence rate of NAFLD in overweight and obese children and adolescents in Germany of up to 30%. The spectrum of NAFLD ranges from pure fatty infiltration (simple steatosis) to inflammation (steatohepatitis, synonymous NASH) to fibrosis and cirrhosis. Age, gender, ethnicity, insulin resistance, and sex steroids are implicated in the pathogenesis of NAFLD in childhood and adolescence. Moreover, NAFLD in the pediatric age group is associated with marked cardiovascular comorbidities. This review focuses on current data regarding epidemiology, pathophysiology, comorbidities, and treatment of NAFLD in children and adolescents.
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Mancini A, Raimondo S, Persano M, Di Segni C, Cammarano M, Gadotti G, Silvestrini A, Pontecorvi A, Meucci E. Estrogens as antioxidant modulators in human fertility. Int J Endocrinol 2013; 2013:607939. [PMID: 24363671 PMCID: PMC3863713 DOI: 10.1155/2013/607939] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 10/28/2013] [Accepted: 10/28/2013] [Indexed: 11/30/2022] Open
Abstract
Among treatments proposed for idiopathic male infertility, antiestrogens, like tamoxifen, play a possible role. On the other hand, oxidative stress is a mechanism well recognized for deleterious effects on spermatozoa function. After reviewing the literature on the effects of estrogens in modulation of antioxidant systems, in both sexes, and in different in vivo and in vitro models, we suggest, also on the basis of personal data, that a tamoxifen treatment could be active via an increase in seminal antioxidants.
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Affiliation(s)
- A. Mancini
- Division of Endocrinology, Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
- *A. Mancini:
| | - S. Raimondo
- Division of Endocrinology, Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - M. Persano
- Division of Endocrinology, Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - C. Di Segni
- Division of Endocrinology, Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - M. Cammarano
- Division of Endocrinology, Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - G. Gadotti
- Division of Endocrinology, Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - A. Silvestrini
- Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy
| | - A. Pontecorvi
- Division of Endocrinology, Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - E. Meucci
- Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy
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20
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Raloxifene hydrochloride as hepatitis C treatment. Ann Hepatol 2013. [DOI: 10.1016/s1665-2681(19)31402-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
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Furusyo N, Ogawa E, Sudoh M, Murata M, Ihara T, Hayashi T, Ikezaki H, Hiramine S, Mukae H, Toyoda K, Taniai H, Okada K, Kainuma M, Kajiwara E, Hayashi J. Raloxifene hydrochloride is an adjuvant antiviral treatment of postmenopausal women with chronic hepatitis C: a randomized trial. J Hepatol 2012; 57:1186-92. [PMID: 22889955 DOI: 10.1016/j.jhep.2012.08.003] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2012] [Revised: 07/26/2012] [Accepted: 08/02/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Early menopause in women with chronic hepatitis C virus (HCV) infection is associated with a low likelihood of a sustained virological response (SVR) in conjunction with their antiviral treatment. This is potentially related to their reduced estrogen secretion. The study was done to determine whether selective estrogen receptor modulator administration might improve the efficacy of the current standard of care (SOC) treatment, pegylated interferon (PegIFN) α2a plus ribavirin (RBV), for postmenopausal women. METHODS One hundred and twenty-three postmenopausal women with genotype 1b chronic hepatitis C were randomly assigned to one of two treatment groups: raloxifene hydrochloride (RLX) (60 mg/day) plus SOC (PegIFNα2a 180 μg/week and RBV 600-1,000 mg/day) (n=62) or SOC only (n=61). Genotyping was performed of the polymorphism in the interleukin-28B (IL28B) gene region (rs8099917) of DNA collected from each patient. RESULTS One RLX-treated patient discontinued RLX because of a systemic rash following 2 weeks of treatment. Twenty-four weeks after treatment, the SVR rate was significantly higher for RLX plus SOC patients (61.3%) than for SOC only patients (34.4%) (p=0.0051). Further, the SVR rate was significantly higher for RLX plus SOC patients with IL28B TT (72.5%) than for SOC only patients with IL28B TT (39.2%) (p=0.0014), but no such relationship was observed in patients carrying the minor IL28B allele. CONCLUSIONS RLX improved the efficacy of SOC in the treatment of postmenopausal women with chronic hepatitis C. RLX shows promise as an adjuvant to the standard antiviral treatment of such patients.
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Affiliation(s)
- Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
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Singh N, Singh N, Singh SK, Singh AK, Kafle D, Agrawal N. A comparative study of antioxidant potential of low density lipoprotein in type 2 diabetic men and women. Indian J Endocrinol Metab 2012; 16:609-611. [PMID: 22837925 PMCID: PMC3401765 DOI: 10.4103/2230-8210.98020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Hyperglycemia plays an important role in etiology of vascular complications like atherosclerosis in diabetes. Oxidative modification of low density lipoprotein (LDL) plays an important role in the progression of atherosclerosis. The aim of the present study is to compare the antioxidant potential (AOP) of LDL in type 2 diabetic men and women. MATERIALS AND METHODS The study was carried out in 80 diabetic subjects and 80 control subjects. The men (40) and women (40) in the diabetic groups were studied separately and matched for age (50-60 years), body mass index (BMI), duration of diabetes, glycosylated hemoglobin, and lipid profile. LDL from the serum sample was precipitated by heparin citrate precipitation method. For the measurement of AOP in LDL, we used xanthine-xanthine oxidase method. RESULTS Our results showed that AOP value was significantly low in diabetic women (P < 0.05) in comparison with diabetic men. CONCLUSION It is therefore suggested that LDL from type 2 diabetic women is more prone for oxidation.
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Affiliation(s)
- Nivedita Singh
- Department of Biochemistry, G. R. Medical College, Gwalior, Madhya Pradesh, India
| | - Neelima Singh
- Department of Biochemistry, G. R. Medical College, Gwalior, Madhya Pradesh, India
| | - Sanjeev K. Singh
- Department of Biochemistry, G. R. Medical College, Gwalior, Madhya Pradesh, India
| | - Ajay K. Singh
- Department of Biochemistry, G. R. Medical College, Gwalior, Madhya Pradesh, India
| | - Deepak Kafle
- Department of Biochemistry, G. R. Medical College, Gwalior, Madhya Pradesh, India
| | - Navneet Agrawal
- Diabetes, Obesity and Thyroid Center, Lalitpur Colony, Gwalior, Madhya Pradesh, India
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Neonatal androgenization exacerbates alcohol-induced liver injury in adult rats, an effect abrogated by estrogen. PLoS One 2011; 6:e29463. [PMID: 22206017 PMCID: PMC3243688 DOI: 10.1371/journal.pone.0029463] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2011] [Accepted: 11/29/2011] [Indexed: 01/09/2023] Open
Abstract
Alcoholic liver disease (ALD) affects millions of people worldwide and is a major cause of morbidity and mortality. However, fewer than 10% of heavy drinkers progress to later stages of injury, suggesting other factors in ALD development, including environmental exposures and genetics. Females display greater susceptibility to the early damaging effects of ethanol. Estrogen (E2) and ethanol metabolizing enzymes (cytochrome P450, CYP450) are implicated in sex differences of ALD. Sex steroid hormones are developmentally regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which controls sex-specific cycling of gonadal steroid production and expression of hepatic enzymes. The aim of this study was to determine if early postnatal inhibition of adult cyclic E2 alters ethanol metabolizing enzyme expression contributing to the development of ALD in adulthood. An androgenized rat model was used to inhibit cyclic E2 production. Control females (Ctrl), androgenized females (Andro) and Andro females with E2 implants were administered either an ethanol or isocalorically-matched control Lieber-DeCarli diet for four weeks and liver injury and CYP450 expression assessed. Androgenization exacerbated the deleterious effects of ethanol demonstrated by increased steatosis, lipid peroxidation, profibrotic gene expression and decreased antioxidant defenses compared to Ctrl. Additionally, CYP2E1 expression was down-regulated in Andro animals on both diets. No change was observed in CYP1A2 protein expression. Further, continuous exogenous administration of E2 to Andro in adulthood attenuated these effects, suggesting that E2 has protective effects in the androgenized animal. Therefore, early postnatal inhibition of cyclic E2 modulates development and progression of ALD in adulthood.
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Chandrasekaran VRM, Periasamy S, Liu LL, Liu MY. 17β-Estradiol protects against acetaminophen-overdose-induced acute oxidative hepatic damage and increases the survival rate in mice. Steroids 2011; 76:118-24. [PMID: 20933533 DOI: 10.1016/j.steroids.2010.09.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2010] [Revised: 09/24/2010] [Accepted: 09/28/2010] [Indexed: 11/17/2022]
Abstract
Acetaminophen overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of 17β-estradiol against acetaminophen-induced acute liver injury and mortality in mice. Male mice were given acetaminophen (p-acetamidophenol; 300 mg/kg; orally) to induce acute liver injury. Acetaminophen significantly increased the levels of aspartate transaminase, alanine transaminase, myeloperoxidase, lipid peroxidation, and glutathione reductase, but it decreased superoxide dismutase, catalase, and glutathione. In addition, acetaminophen-induced mortality began 4h post-treatment, and all mice died within 9h. 17β-Estradiol (200 μg/kg; i.p.) protected against acetaminophen-induced oxidative hepatic damage by inhibiting neutrophil infiltration and stimulating the antioxidant defense system. However, 17β-estradiol did not affect acetaminophen-induced glutathione depletion or increased glutathione reductase activity. We conclude that 17β-estradiol specifically attenuates acute hepatic damage and decreases mortality in acetaminophen-overdosed male mice.
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25
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Mancini A, Festa R, Di Donna V, Leone E, Littarru GP, Silvestrini A, Meucci E, Pontecorvi A. Hormones and antioxidant systems: role of pituitary and pituitary-dependent axes. J Endocrinol Invest 2010; 33:422-33. [PMID: 20631494 DOI: 10.1007/bf03346615] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Oxidative stress, a condition defined as unbalancing between production of free radicals and antioxidant defenses, is an important pathogenetic mechanism in different diseases. Despite the abundant literature, many aspects of hormone role in regulating antioxidant synthesis and activity still remain obscure. Therefore, we reviewed experimental data, in vivo and in vitro, about the effects of the different pituitary- dependent axes on antioxidant levels, trying to give a broad view from hormones which also have antioxidant properties to the classic antioxidants, from the lipophilic antioxidant Coenzyme Q10, strictly related to thyroid function, to total antioxidant capacity, a measure of non-protein non-enzymatic antioxidants in serum and other biological fluids. Taken together, these data underline the importance of oxidative stress in various pituitary-dependent disorders, suggesting a possible clinical usefulness of antioxidant molecules.
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Affiliation(s)
- A Mancini
- Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy.
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Yang F, Yin Y, Wang F, Zhang L, Wang Y, Sun S. An altered pattern of liver apolipoprotein A-I isoforms is implicated in male chronic hepatitis B progression. J Proteome Res 2010; 9:134-43. [PMID: 19788185 DOI: 10.1021/pr900593r] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Chronic hepatitis B (CHB) appears to progress more rapidly in males than in females, and CHB-related hepatic cirrhosis and hepatocellular carcinoma are predominately diseases that tend to occur in men and postmenopausal women. To obtain more insight into the underlying mechanisms of gender disparity of CHB progress, two-dimensional difference gel electrophoresis was employed to compare liver proteome of C57BL/6 and HBV transgenic (HBV-Tg) mice both in male and female groups. We identified 8 differently expressed proteins in male HBV-Tg mice and 12 in female HBV-Tg mice. Apolipoprotein A-I (Apo A-I) was found to be down-regulated in male and female HBV-Tg mouse liver. It is more interesting that the pattern of liver Apo A-I isoforms was altered in male HBV-Tg mice but not in female HBV-Tg mice. Our further results indicated that the basic Apo A-I isoform, based on pI positions from serum 2-dimensional Western blotting, increased in male CHB patient sera but not in female CHB patient sera. Finally, we identified that the oxidative modification Apo A-I mainly reside in basic isoform. This pattern of selectively modified Apo A-I isoforms may be considered as a pathological hallmark that may extend our knowledge of the molecular pathogenesis of CHB progression.
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Affiliation(s)
- Fu Yang
- Department of Medical Genetics, Second Military Medical University, Shanghai, China
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Pérez-Torres I, Roque P, El Hafidi M, Diaz-Diaz E, Baños G. Association of renal damage and oxidative stress in a rat model of metabolic syndrome. Influence of gender. Free Radic Res 2010; 43:761-71. [DOI: 10.1080/10715760903045296] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Dlugosz A, Roszkowska A, Zimmer M. Oestradiol protects against the harmful effects of fluoride more by increasing thiol group levels than scavenging hydroxyl radicals. Basic Clin Pharmacol Toxicol 2009; 105:366-73. [PMID: 19799602 DOI: 10.1111/j.1742-7843.2009.00411.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The aim of the study was to investigate the role of oestrogens in free radical detoxication upon exposure to fluoride. Interactions between xenobiotics and oestrogens need to be investigated, especially as many chemicals interact with the oestrogen receptor. It is still unknown whether free radical-generating xenobiotics can influence the antioxidative ability of oestradiol (E(2)). In an in vitro examination of human placental mitochondria, thiobarbituric active reagent species (TBARS), hydroxyl radical ((*)OH) generation and protein thiol (-SH) groups were detected. 17beta-E(2) was examined in physiological (0.15-0.73 nM) and experimental (1-10 microM) concentrations and sodium fluoride (NaF) in concentrations of 6-24 microM. E(2) in all the concentrations significantly decreased lipid peroxidation measured as the TBARS level, in contrast to NaF, which increased lipid peroxidation. Lipid peroxidation induced by NaF was decreased by E(2). The influence of E(2) on (*)OH generation was not very significant and depended on the E(2 )concentration. The main mechanism of E(2) protection in NaF exposure appeared to be connected with the influence of E(2 )on thiol group levels, not (*)OH scavenging ability. The E(2) in concentrations 0.44-0.73 nM and 1-10 microM significantly increased the levels of -SH groups, in contrast to NaF, which significantly decreased them. E(2) at every concentration reversed the harmful effects of NaF on -SH group levels. No unfavourable interactions in the influence of E(2) and NaF on TBARS production, (*)OH generation, or -SH group levels were observed. The results suggest that postmenopausal women could be more sensitive to NaF-initiated oxidative stress.
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Affiliation(s)
- Anna Dlugosz
- Department of Toxicology, Wroclaw Medical University, Traugutta, Wroclaw, Poland.
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Estrogen deficiency-induced alterations of vascular MMP-2, MT1-MMP, and TIMP-2 in ovariectomized rats. Am J Hypertens 2009; 22:27-34. [PMID: 19023275 DOI: 10.1038/ajh.2008.306] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Matrix metalloproteinases (MMPs) activity may modulate hypertension-related accumulation of extracellular matrix (ECM) in arteries. We tested whether estrogen deficiency induces alterations of vascular collagen, MMP-2, membrane-type 1-MMP (MT1-MMP), or tissue inhibitor of metalloproteinases-2 (TIMP-2) expression in ovariectomized rats, which may be associated with postmenopausal hypertension. METHODS Estrogen deficiency was induced by ovariectomy (Ovx) in female rats. Time-course changes of aortic MMPs protein expression were evaluated. Treatment with tempol or aminoguanidine was used to examine the role of oxidative stress and nitric oxide (NO) on these changes. RESULTS The level of the active-form MMP-2 was markedly reduced during 1-4 weeks after Ovx, with a significant increase in collagen accumulation and increased MT1-MMP expression. Although active-form MMP-2 and collagen progressively returned to normal levels, the markedly increased collagen deposition appeared again at 8 weeks and persisted until 12 weeks, followed by induction of MMP-2 and MT1-MMP at 12 weeks. The TIMP-2 level reduced for 2 weeks after Ovx, but soon returned to normal. Treatment with 17beta-estradiol (E(2)), tempol, or aminoguanidine for 6 weeks prevented Ovx-induced blood pressure elevation and apparently reversed the MMPs changes. CONCLUSIONS In an initial period, E(2) deficiency induces a reduction of active-form MMP-2 leading to collagen accumulation, and induction of MT1-MMP, which may be a compensatory response to degrade collagen. At a latter stage, the concurrent elevation of active-form MMP-2 and MT1-MMP expression may be adaptive responses to regulate ECM composition in the vascular wall. Oxidative stress and NO contribute to activity modulation of vascular MMPs in Ovx rats.
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Abstract
Acute bouts of aerobic and anaerobic exercise can induce a state of oxidative stress, as indicated by an increase in oxidized molecules in a variety of tissues and body fluids. The extent of oxidation is dependent on the exercise mode, intensity, and duration, and is specifically related to the degree of oxidant production. Findings of increased oxidative stress have been reported for both healthy and diseased subjects following single bouts of exercise. While acute exercise has the ability to induce an oxidative stress, this same exercise stimulus appears necessary to allow for an upregulation in endogenous antioxidant defenses. This chapter presents a summary of exercise-induced oxidative stress.
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Affiliation(s)
- Richard J Bloomer
- Department of Health and Sport Sciences, The University of Memphis, Memphis, Tennessee 38152, USA.
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Barshop NJ, Sirlin CB, Schwimmer JB, Lavine JE. Review article: epidemiology, pathogenesis and potential treatments of paediatric non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; 28:13-24. [PMID: 18397387 DOI: 10.1111/j.1365-2036.2008.03703.x] [Citation(s) in RCA: 97] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common cause of paediatric liver disease. Similar to NAFLD in adults, NAFLD in children is associated with obesity and insulin resistance and requires liver histology for diagnosis and staging. However, significant histological differences exist between adult and paediatric NAFLD to warrant caution in extrapolation of adult data. AIM To review the available data on the epidemiology, pathogenesis, diagnosis and treatment of paediatric NAFLD. METHODS Relevant articles were identified by Medline searches using the keywords: nonalcoholic fatty liver disease, steatohepatitis, obesity and children. RESULTS The rise in childhood obesity has been accompanied by an increase in paediatric NAFLD. Age, gender and race/ethnicity are significant determinants of risk, and sex hormones, insulin sensitivity and adipocytokines are implicated in the pathogenesis of paediatric NAFLD. There is no consensus for treatment of NAFLD; however, data suggest that diet, exercise and some pharmacological therapies may be of benefit. CONCLUSIONS To evaluate and effectively treat paediatric NAFLD, the pathophysiology and natural history of the disease should be clarified and non-invasive methods for screening, diagnosis, and longitudinal assessment developed. Randomized, controlled, double-blind trials of pharmacological therapies in children with biopsy-proven disease are necessary.
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Affiliation(s)
- N J Barshop
- Department of Pediatrics, University of California, San Diego, CA, USA
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Prokai-Tatrai K, Perjesi P, Rivera-Portalatin NM, Simpkins JW, Prokai L. Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative. Steroids 2008; 73:280-8. [PMID: 18068745 PMCID: PMC2317824 DOI: 10.1016/j.steroids.2007.10.011] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2007] [Revised: 08/11/2007] [Accepted: 10/24/2007] [Indexed: 10/22/2022]
Abstract
Antioxidant action is an important component of the complex neuroprotective effect of estrogens. Combining theoretical prediction and subsequent experimental confirmation by chemical and in vitro paradigms, this study focused on the mechanistic aspects of hydroxyl radical scavenging by 17beta-butoxy-1,3,5(10)-estratrien-3-ol, a synthetic derivative of 17beta-estradiol with increased potency to inhibit lipid peroxidation and reduced affinity to estrogen-receptors compared to the endogenous hormone. In the process that acts as a "chemical shield," the phenolic A-ring turns into 10beta-hydroxy-17beta-butoxy-1,3,5(10)-estratrien-3-one, a non-aromatic para-quinol, upon capturing hydroxyl radicals, which results in the complete loss of estrogen-receptor affinity and antioxidant activity. However, the parent compound is apparently recovered in brain tissue from this para-quinol via enzyme-catalyzed NAD(P)H-dependent reductive aromatization without causing oxidative stress. Taken together, our report argues for a previously unrecognized antioxidant cycle for estrogen-derived compounds.
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Affiliation(s)
- Katalin Prokai-Tatrai
- Department of Pharmacology and Neuroscience, UNT Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA
| | - Pal Perjesi
- Institute of Pharmaceutical Chemistry, University of Pecs, Pecs, Hungary
| | - Nilka M. Rivera-Portalatin
- Department of Molecular Biology and Immunology, UNT Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA
| | - James W. Simpkins
- Department of Pharmacology and Neuroscience, UNT Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA
| | - Laszlo Prokai
- Department of Molecular Biology and Immunology, UNT Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA
- Corresponding author. Tel.: +1-817-735-2206; Fax: +1-817-735-2118; E-mail address: (L. Prokai)
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Anbazhagan V, Kandavelu V, Kathiravan A, Renganathan R. Investigation on the fluorescence quenching of 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) by certain estrogens and catechols. J Photochem Photobiol A Chem 2008. [DOI: 10.1016/j.jphotochem.2007.06.026] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Shankar A, Li J, Klein BEK, Nieto FJ, Klein R. Serum gamma-glutamyltransferase level and peripheral arterial disease. Atherosclerosis 2007; 199:102-9. [PMID: 18037420 DOI: 10.1016/j.atherosclerosis.2007.10.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2007] [Revised: 09/27/2007] [Accepted: 10/12/2007] [Indexed: 10/22/2022]
Abstract
OBJECTIVE We examined the association between increasing serum GGT levels and PAD in the US general population. METHODS Cross-sectional study among 3941 National Health and Nutrition Examination Survey 1999-2002 participants aged >or=40 years. Main outcome-of-interest was PAD defined as ankle-brachial index <0.9 (n=219). RESULTS Overall, serum GGT levels were positively associated with PAD among men but not women (p-interaction=0.0421). Among men, the multivariable odds ratio (OR) [95% confidence intervals (CI)] comparing the highest quartile of serum GGT (>35U/L) to the lowest quartile (<16U/L) was 4.25 (1.65-10.94); p-trend=0.0008. Also the observed positive association between GGT quartiles and PAD among men was predominantly present among non-Hispanic whites and current nondrinkers (multivariable OR [95% CI] comparing the highest quartile of serum GGT to the lowest quartile was 10.59 [2.31-48.55]; p-trend=0.0104). In contrast among women, the multivariable OR (95% CI) comparing the highest quartile of serum GGT to the lowest quartile was 0.76 (0.41-1.41); p-trend=0.8308. CONCLUSIONS There was a positive association between serum GGT level and PAD among men, particularly non-Hispanic white and nondrinker men, but not among women. Future prospective studies are required to clarify the temporal nature of this relationship and to confirm the observed gender-specific nature of this association.
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Affiliation(s)
- Anoop Shankar
- Department of Community, Occupational, and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Block MD3, 16 Medical Drive, Singapore 117597, Singapore.
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Shimizu I, Kohno N, Tamaki K, Shono M, Huang HW, He JH, Yao DF. Female hepatology: Favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol 2007; 13:4295-305. [PMID: 17708600 PMCID: PMC4250853 DOI: 10.3748/wjg.v13.i32.4295] [Citation(s) in RCA: 100] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection is the most common cause of hepatic fibrosis and hepatocellular carcinoma (HCC), mainly as a result of chronic necroinflammatory liver disease. A characteristic feature of chronic hepatitis B infection, alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD) is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which, in turn, activates hepatic stellate cells (HSCs). HSCs are the primary target cells for inflammatory and oxidative stimuli, and these cells produce extracellular matrix components. Chronic hepatitis B appears to progress more rapidly in males than in females, and NAFLD, cirrhosis and HCC are predominately diseases that tend to occur in men and postmenopausal women. Premenopausal women have lower hepatic iron stores and a decreased production of proinflammatory cytokines. Hepatic steatosis has been observed in aromatase-deficient mice, and has been shown to decrease in animals after estradiol treatment. Estradiol is a potent endogenous antioxidant which suppresses hepatic fibrosis in animal models, and attenuates induction of redox sensitive transcription factors, hepatocyte apoptosis and HSC activation by inhibiting a generation of reactive oxygen species in primary cultures. Variant estrogen receptors are expressed to a greater extent in male patients with chronic liver disease than in females. These lines of evidence suggest that the greater progression of hepatic fibrosis and HCC in men and postmenopausal women may be due, at least in part, to lower production of estradiol and a reduced response to the action of estradiol. A better understanding of the basic mechanisms underlying the sex-associated differences in hepatic fibrogenesis and carciogenesis may open up new avenues for the prevention and treatment of chronic liver disease.
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Affiliation(s)
- Ichiro Shimizu
- Department of Digestive and Cardiovascular Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
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Krishnan N, Vecera J, Kodrík D, Sehnal F. 20-Hydroxyecdysone prevents oxidative stress damage in adult Pyrrhocoris apterus. ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY 2007; 65:114-24. [PMID: 17570141 DOI: 10.1002/arch.20182] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2023]
Abstract
Injections of 38 pmol paraquat (1,1'-dimethyl-4,4'-bypyridilium) into adult Pyrrhocoris apterus (average body weight 29.6 mg in males and 36.9 mg in females) caused a significant elevation of lipid peroxidation and protein carbonylation and a decline of membrane fluidity in the microsomal brain fraction. Another manifestation of oxidative stress was a depletion of the reduced glutathione pool and reduction of the gamma-glutamyl transpeptidase activity in the brain extracts. The damaging action of paraquat on the brain was counteracted by simultaneous injection of 1 pmol 20-hydroxyecdysone (20E). 20E restrained lipid peroxidation and the formation of protein carbonyls, ameliorated changes in microsomal membrane fluidity, enhanced the level of reduced glutathione, and upregulated the activity of gamma-glutamyl transpeptidase. At the organismic level, 20E curtailed three detrimental effects caused by paraquat injection: the disappearance of a blood protein, the suppression of fecundity and egg hatchability, and the shortening of adult life span. The data showed that 20E provided a systemic antioxidant protection but the significance of endogenous ecdysteroids in the management of oxidative stress remains to be shown.
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Affiliation(s)
- Natraj Krishnan
- Department of Physiology, Institute of Entomology, Biology Centre, Czech Academy of Sciences, Ceské Budejovice, Czech Republic
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Abstract
Hepatitis C virus infections are recognized as a major causative factor of chronic liver disease. A characteristic feature of chronic hepatitis C, alcoholic liver disease and non-alcoholic fatty liver disease is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which, in turn, activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory and oxidative stimuli, and to produce extracellular matrix components. Based on available clinical information, chronic hepatitis C appears to progress more rapidly in men than in women, and cirrhosis is predominately a disease of men and postmenopausal women. Estradiol is a potent endogenous antioxidant. Hepatic steatosis was reported to become evident in an aromatase-deficient mouse and was diminished in animals after treatment with estradiol. Our previous studies showed that estradiol suppressed hepatic fibrosis in animal models, and attenuated HSC activation by suppressing the generation of reactive oxygen species in primary cultures. Variant estrogen receptors were found to be expressed to a greater extent in male patients with chronic liver disease than in female subjects. A better understanding of the basic mechanisms underlying the gender-associated differences observed in the progression of chronic liver disease would provide valuable information relative to the search for effective antifibrogenic therapies.
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Affiliation(s)
- Ichiro Shimizu
- Department of Digestive and Cardiovascular Medicine, Tokushima University Graduate School of Medicine, Tokushima, Japan
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Castillo C, Salazar V, Ariznavarreta C, Vara E, Tresguerres JAF. Effect of isoflavone administration on age-related hepatocyte changes in old ovariectomized femal Wistar rats. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2006; 13:468-76. [PMID: 16785039 DOI: 10.1016/j.phymed.2005.03.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2004] [Accepted: 03/22/2005] [Indexed: 05/10/2023]
Abstract
Aging seems to be due to the accumulation of oxidative damage in cells and molecules. On the other hand, menopause and ovariectomy induce deleterious effects on different organs and systems that have been shown to be counteracted by estrogens and in a not so evident form also with phytoestrogens. The present study has investigated whether the administration of a commercial soy extract that contains approximately 10% isoflavones was able to modify some parameters related to oxidative stress and inflammation in hepatocytes isolated from old ovariectomized female Wistar rats. Eighteen 22-month-old animals that had been previously ovariectomized at 12 months of age were divided into four groups: ovariectomized control rats, estradiol-treated ovariectomized females and ovariectomized rats treated with isoflavones. Six intact female rats of 2 months of age were used as reference group. Hepatocytes were isolated and cultured, and carbon monoxide (CO) and nitric oxide (NO) release, as well as adenosyl triphosphate (ATP), cyclic guanosyl monophosphate (cGMP), phosphatidylcholine (PC) and lipid peroxide (LPO) content of cells were evaluated. Uterus was also removed and weighed. Hepatocytes isolated from old ovariectomized rats showed a decrease in ATP content as compared to young animals. Age also induced an increase in LPO cell content. NO, CO and cGMP were augmented with age, and PC synthesis showed a dramatic reduction. Treatment with either estradiol or isoflavones were able to improve all the mentioned parameters altered in hepatocytes isolated from old ovariectomized rats, and the magnitude of the improvement was similar for both treatments. Ovariectomy induced a significant reduction in uterine weight, which was significantly counteracted by estradiol treatment but not by isoflavone administration. In conclusion, the administration of a soy extract containing isoflavones seems to prevent oxidative changes in hepatocytes isolated from old ovariectomized female rats, without modifying uterus weight.
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Affiliation(s)
- C Castillo
- Laboratory of Experimental Endocrinology, Department of Physiology, School of Medicine, Complutense University, Madrid, Spain
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Chetty CS, Vemuri MC, Reddy GR, Suresh C. Protective effect of 17-beta-estradiol in human neurocellular models of lead exposure. Neurotoxicology 2006; 28:396-401. [PMID: 16678263 DOI: 10.1016/j.neuro.2006.03.012] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2005] [Accepted: 03/10/2006] [Indexed: 11/16/2022]
Abstract
The developing nervous system has long been recognized as a primary target site for lead (Pb)-induced toxicity. Pb-exposure causes cognitive dysfunction, growth retardation, hyperactivity and neurochemical deficits in animals and humans. In the present study the effects of 17-beta-estradiol on human SH-SY5Y neuroblastoma cells in culture exposed to low-levels of Pb were assessed. The cells were exposed to Pb (0.01-10 microM) for 48 h and cell proliferation was determined by the MTT reduction assay. Pb significantly inhibited the proliferation and growth of neuroblastoma cells in a concentration-dependent manner. A 50% inhibition (IC50) in the proliferation of cells was observed with 5 microM Pb. Exposure of cells to Pb (5 microM) for 48 h resulted in a significant increase (+732% of control) in caspase-3 activity, an indicator of apoptosis and total cellular prostaglandin E2 level (+1180% of control), marker of programmed cell death/neuronal cell loss. Pretreatment with 17-beta-estradiol (10 nM) effectively blocked the effects of Pb on caspase-3 activity but not prostaglandin E2 level. Further, Pb but not 17-beta-estradiol in a concentration (0.1-10 microM)-dependent manner effectively decreased (38-84%) the cellular concentration of glutathione (GSH), an important intracellular antioxidant. However, the effect of Pb on GSH level was effectively blocked when pretreated with 17-beta-estradiol. The data indicate that even low concentrations of Pb can be detrimental and potentially toxic to the developing brain. In conclusion, these results suggest that at least some of the neurotoxic effects of Pb may be mediated by apoptosis, which by pretreatment with 17-beta-estradiol can be prevented. This study further confirms previous reports of 17-beta-estradiol acting as a neuroprotective and antiapoptotic agent during induced toxic stress conditions.
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Lam KK, Lee YM, Hsiao G, Chen SY, Yen MH. Estrogen therapy replenishes vascular tetrahydrobiopterin and reduces oxidative stress in ovariectomized rats. Menopause 2006; 13:294-302. [PMID: 16645543 DOI: 10.1097/01.gme.0000182806.99137.5e] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE We investigated whether the effect of estrogen therapy on vascular endothelial function is mediated through increasing the bioavailability of tetrahydrobiopterin (BH4) and associated antioxidant capacity in ovariectomized (Ovx) rats. DESIGN Aortas of sham-operated, Ovx, and Ovx plus estrogen therapy (Ovx + ET) female Sprague-Dawley rats were used to measure vascular reactivity. Plasma levels of nitric oxide (NO) metabolites, total antioxidant capacity, aortic superoxide anion (O2.), and BH4 contents were determined. RESULTS Vascular reactivity, assessed on isolated aortic segments, indicated that phenylephrine-induced contraction in the Ovx group was significantly greater than that in the sham and Ovx + ET groups. The vasodilator responses to acetylcholine (10 to 10 M) and L-arginine (L-Arg; 10 M) in the sham and Ovx + ET groups were significantly greater than those in the Ovx group. Pretreatment with BH4 (10 M) enhanced the vasodilator responses to L-Arg in the Ovx group compared with the untreated Ovx group. An inhibitor of BH4 synthesis, 2,4-diamino-6-hydroxypyrimidine (2 mM), significantly attenuated the vasodilator response to L-Arg in the sham and Ovx + ET groups. In addition, Ovx significantly increased O2. production in aortic tissues and decreased plasma NO metabolites levels, whereas ET significantly prevented these effects. Pretreatment with BH4 also significantly decreased aortic O2. production in the Ovx group; both plasma total antioxidant capacity and aortic BH4 contents in the Ovx group decreased significantly compared with those in the sham group, which were also improved by ET. There were no significant differences in the protein expression of endothelial NO synthase in aortas in these groups. CONCLUSIONS ET increases the availability of vascular BH4 to attenuate O2. production and restores total antioxidant capacity, leading to improved NO-mediated vasodilation in Ovx rats.
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Affiliation(s)
- Kwok-Keung Lam
- Department of Pharmacology, Taipei Medical College, Taipei, Taiwan
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Signorelli SS, Neri S, Sciacchitano S, Pino LD, Costa MP, Marchese G, Celotta G, Cassibba N, Pennisi G, Caschetto S. Behaviour of some indicators of oxidative stress in postmenopausal and fertile women. Maturitas 2006; 53:77-82. [PMID: 16325025 DOI: 10.1016/j.maturitas.2005.03.001] [Citation(s) in RCA: 100] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2004] [Revised: 01/29/2005] [Accepted: 03/03/2005] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Unsaturated fatty acids are known to have a crucial role in the pathogenesis of atherosclerosis. They are very sensitive to oxidation caused by excess free oxygen radicals and the consequent oxidative status, and it is well known that lipid and lipoprotein metabolism is markedly altered in postmenopausal women. Oxidative stress is involved in the pathophysiology of atherosclerosis and our study aim was to assess the presence of such stress in postmenopausal women. DESIGN One hundred and one women were enrolled in the study. Fifty were fertile (32.5+/-1.1 years) with regular menses and fifty-one were postmenopausal women (52.1+/-1.3 years). None of the study cohort had ever used hormone replacement therapy. Malonaldehyde (MDA), 4-hydroxynenal (4-HNE), oxidized lipoproteins (ox LDL) and glutathione peroxidase (GSH-PX) values were determined as we believe they reveal oxidative stress. RESULTS MDA, 4-HNE and ox LDL concentrations were higher in postmenopausal than fertile women (p<0.001), while GSH-PX concentrations were significantly higher in fertile women than in postmenopausal subjects (p<0.001). CONCLUSIONS Our data revealed the presence of oxidative stress in postmenopausal women.
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Affiliation(s)
- Salvatore Santo Signorelli
- Department of Internal Medicine and Systemic Disease, Section of Medical Angiology, Faculty of Medicine, University of Catania, Via Firenze 123, 95020 Acicastello (CT), Italy.
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Cegelski L, Rice CV, O'Connor RD, Caruano AL, Tochtrop GP, Cai ZY, Covey DF, Schaefer J. Mapping the locations of estradiol and potent neuroprotective analogues in phospholipid bilayers by REDOR. Drug Dev Res 2006. [DOI: 10.1002/ddr.20048] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Yajun Z, Hongshan C, Baoxi S, Dengbing Y, Jianhua S, Xinshun G, Li Y, Yi C. Translocation of Bax in rat hepatocytes cultured with ferric nitrilotriacetate. Life Sci 2005; 76:2763-72. [PMID: 15808878 DOI: 10.1016/j.lfs.2004.07.035] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2004] [Accepted: 07/02/2004] [Indexed: 11/16/2022]
Abstract
Hepatic fibrosis occurs after many years of iron overload in liver. An effective iron deposition model induced by ferric nitrilotriacetate (FeNTA) in cultured rat hepatocytes was assumed. It has been shown that treatment of rat hepatocytes with FeNTA lead to oxidative stress and hepatocyte apoptosis. Hepatocyte apoptosis can promote liver fibrosis. The mechanisms of hepatocyte apoptosis induced by FeNTA have not yet been fully elucidated. The present study demonstrated that FeNTA-induced hepatocyte apoptosis was related to Bax translocation, cytochrome c release, and caspase-3 activation.
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Affiliation(s)
- Zhou Yajun
- Department of Biochemistry and Molecular Biology, Medical College, Nan Tong University 226001, Jiangsu Province, PR China.
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Kaya H, Ozkaya O, Sezik M, Arslanoglu E, Yilmaztepe A, Ulukaya E. Effects of raloxifene on serum malondialdehyde, erythrocyte superoxide dismutase, and erythrocyte glutathione peroxidase levels in healthy postmenopausal women. Maturitas 2005; 50:182-8. [PMID: 15734599 DOI: 10.1016/j.maturitas.2004.05.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2004] [Revised: 05/17/2004] [Accepted: 05/24/2004] [Indexed: 11/21/2022]
Abstract
OBJECTIVE To investigate the relationship between raloxifene administration and serum malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPx) levels in healthy postmenopausal women. METHODS In a randomized and placebo-controlled design, 80 women received either 60 mg/day raloxifene or placebo for 24 weeks. MDA, SOD, and GPx levels were assessed at 0,4,12, and 24 weeks. Wilcoxon signed-rank test and Mann-Whitney U test were used for comparisons. RESULTS Six women in the treatment arm and eight women in the placebo group discontinued the study. Mean serum MDA levels were significantly (p = 0.001) decreased from 11.4 nmol/ml at baseline to 8.9 nmol/ml at week 12 with raloxifene treatment. Mean erythrocyte SOD activity was significantly (p = 0.02) reduced from 1472 U/g Hb at baseline to 1173 U/g Hb at week 12 following raloxifene administration. Lowered serum MDA and erythrocyte SOD levels persisted during treatment. On contrary, erythrocyte GPx levels did not change significantly with raloxifene administration. CONCLUSIONS Raloxifene (60 mg/day) lowers serum MDA levels and erythrocyte SOD activity in postmenopausal women after 12 weeks of treatment. The clinical implications of these findings need to be determined.
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Affiliation(s)
- Hakan Kaya
- Department of Obstetrics and Gynecology, School of Medicine, Suleyman Demirel University, Isparta, Turkey
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Kang JS, Wanibuchi H, Morimura K, Puatanachokchai R, Salim EI, Hagihara A, Seki S, Fukushima S. Enhancement by estradiol 3-benzoate in thioacetamide-induced liver cirrhosis of rats. Toxicol Sci 2005; 85:720-6. [PMID: 15716488 DOI: 10.1093/toxsci/kfi113] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
As part of an investigation on the role of estrogen in liver disease, we tested the effects of estradiol-3-benzoate (EB) in the thioacetamide (TAA)-induced rat liver cirrhosis model. Male F344 rats (n = 100) were divided into six groups. Animals of groups 1-4 received TAA (0.03% in drinking water) for 12 weeks, and groups 5 and 6 served as controls without TAA. For the exposure period, EB pellets were implanted subcutaneously to give doses of 0 (groups 1 and 5), 1 (group 2), 10 (group 3), and 100 mug (groups 4 and 6) simultaneously. All animals were sacrificed at week 12. Significant increase of liver cirrhosis, liver weight, collagen content, and lipid peroxidation in the livers was evident in groups 3 and 4 (p < 0.05) compared with group 1. Formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was significantly elevated in group 4 (p < 0.01), along with expression of alpha-smooth muscle actin (alpha-SMA) and stellate cell activation-associated protein (STAP), as determined by RT-PCR analysis (p < 0.01). However, there were no differences in liver weight, collagen content, lipid peroxidation, 8-OHdG formation, and alpha-SMA and STAP mRNA expression between groups 5 and 6. We conclude that EB treatment enhances TAA-induced cirrhosis, associated with increase of oxidative stress and activation of hepatic stellate cells.
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Affiliation(s)
- Jin Seok Kang
- Department of Pathology, Graduate School of Medicine, Osaka City University Medical School, Asahi-machi, Osaka 545-8585, Japan
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Castillo C, Salazar V, Ariznavarreta C, Vara E, Tresguerres JAF. Effect of growth hormone and estrogen administration on hepatocyte alterations in old ovariectomized female wistar rats. Endocrine 2005; 26:11-8. [PMID: 15805580 DOI: 10.1385/endo:26:1:011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2004] [Revised: 12/17/2004] [Accepted: 12/17/2004] [Indexed: 12/21/2022]
Abstract
Aging could be due to the accumulation of oxidative damage. On the other hand, growth hormone (GH) and estrogen deficiency induce deleterious effects on different tissues, and hormonal replacement could counteract these effects. We have investigated whether GH and estrogen administration modify some parameters related to oxidative stress and inflammation in hepatocytes isolated from old ovariectomized female rats. Twenty-two month-old ovariectomized animals were divided into control rats, rats treated with GH, rats treated with estradiol, and rats treated with GH+estradiol. Two-month-old intact female rats were used as young reference group. Hepatocytes were isolated, cultured, and CO and NO release, ATP, cyclic-guanosyl monophosphate (cGMP), and lipid peroxide (LPO) content of cells, as well as phosphatidylcholine (PC)synthesis, were measured. Hepatocytes isolated from old ovariectomized rats showed a decrease in ATP content and PC synthesis compared to young rats. Age also induced an increase in LPO, NO, CO, and cGMP. Treating old rats with GH significantly increased ATP and reduced CO and cGMP levels. Estradiol administration improved all the parameters that were altered. Co-administration of GH and estrogens induced a more marked effect than estrogens alone only in cGMP content. In conclusion, administration of estrogens to old ovariectomized females seemed to prevent oxidative changes in hepatocytes, whereas the effect of GH is not so evident.
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Affiliation(s)
- Carmen Castillo
- Laboratory of Experimental Endocrinology, Department of Physiology, School of Medicine, Complutense University, Madrid, Spain
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Thibodeau PA, Gozin A, Gougerot-Pocidalo MA, Pasquier C. Redox modulation of tyrosine phosphorylation-dependent neutrophil adherence to endothelial cells. Radiat Phys Chem Oxf Engl 1993 2005. [DOI: 10.1016/j.radphyschem.2004.04.139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Jung ME, Rewal M, Perez E, Wen Y, Simpkins JW. Estrogen protects against brain lipid peroxidation in ethanol-withdrawn rats. Pharmacol Biochem Behav 2004; 79:573-86. [PMID: 15582030 DOI: 10.1016/j.pbb.2004.09.007] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2004] [Revised: 09/09/2004] [Accepted: 09/10/2004] [Indexed: 11/18/2022]
Abstract
This study examined whether 17beta-estradiol (E2) administration protects against ethanol withdrawal (EW)-associated oxidative insults by assessing oxidative markers thiobarbituric-acid-reacting-substances (TBARS). Ovariectomized rats implanted with E2 (EW/E2) or oil pellets (EW/Oil) received chronic ethanol (7.5% wt./vol., 5 weeks) or control dextrin diet (Dextrin/Oil). At 24 or 48 h of EW, rats were tested for overt EW signs and the cerebellum, hippocampus, and cortex were prepared for TBARS assessment in the presence and absence of FeCl3. For control experiments, we assessed E2 effects on blood ethanol concentrations and TBARS levels during ethanol exposure prior to EW. The EW/Oil group showed enhanced endogenous- and FeCl3-stimulated membrane TBARS levels in the cerebellum and hippocampus in a manner inhibited by E2 treatment. There was a relationship between the severity of EW and elevation of TBARS levels, particularly in the cerebellum. The enhanced TBARS levels at 24 h of EW appeared to diminish at 48 h in the hippocampus, but persisted in the cerebellum. E2 treatment did not alter blood ethanol concentrations and ethanol exposure alone did not enhance TBARS levels. These data suggest that EW rather than ethanol enhances brain lipid peroxidation that is transient and brain-region specific. Estrogens protect against the brain lipid peroxidation in a manner independent of blood ethanol concentrations.
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Affiliation(s)
- Marianna E Jung
- Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, USA.
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Castillo C, Salazar V, Ariznavarreta C, Vara E, Tresguerres JAF. Effect of recombinant human growth hormone on age-related hepatocyte changes in old male and female Wistar rats. Endocrine 2004; 25:33-9. [PMID: 15545704 DOI: 10.1385/endo:25:1:33] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2004] [Revised: 09/08/2004] [Accepted: 09/17/2004] [Indexed: 01/01/2023]
Abstract
Aging induces changes in several organs, such as the liver, and this process might be due to damage caused by free radicals and inflammatory mediators. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis shows a reduction with age, and this fact could be associated with some age-related changes. The aim of this study was to investigate the effect of GH administration on age-induced alterations in hepatocytes. Two and twenty two month-old male and female Wistar rats were used. Old rats were treated with human recombinant GH for 10 wk. At the end of the treatment, hepatocytes were isolated from the liver and cultured, and different parameters were measured in cells and medium. Plasma IGF-1 was also measured. Aging significantly decreased plasma IGF-1 in males. In females, plasma IGF-1 was also reduced, but not significantly. GH treatment restored plasma IGF-1 levels to values similar to young males. Aging was associated with a significant increase in lipid peroxidation (LPO), nitric oxide (NO), carbon monoxide (CO) and cyclic guanosyl-monophosphate (cGMP), as well as a reduction in adenosyl triphosphate (ATP) and phosphatidylcholine (PC) synthesis. GH administration partially prevented all these changes in males. In females, some of the parameters were significantly improved by GH (ATP, CO, cGMP), while others showed a tendency to improvement, although differences did not reach significance. In conclusion, GH administration could exert beneficial effects against age-related changes in hepatocytes, mainly in males.
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Affiliation(s)
- Carmen Castillo
- Laboratory of Experimental Endocrinology, Department of Physiology, School of Medicine, Complutense University, Madrid, Spain
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Thibodeau PA, Pasquier C, Gougerot-Pocidalo MA. Measurement of copper(I) formation as a test for the stability of catecholestrogens and methoxyestrogens in solution. Steroids 2004; 69:419-23. [PMID: 15219791 DOI: 10.1016/j.steroids.2004.03.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2003] [Revised: 03/19/2004] [Accepted: 03/25/2004] [Indexed: 11/21/2022]
Abstract
The biological effects of estrogens seem to be divided into three mechanisms of action: (1) the transcriptional action by the estrogen-estrogen receptor (ER) complex, (2) the non-genomic mechanism through ERs in cell membranes, and (3) the ER-independent mechanism. The latter mechanism has been attributed to be mediated by the basic chemical properties of estradiol (E2) metabolites, which seems to include their pro- and anti-oxidant properties. Therefore, in order to study the ER-independent actions of the E2 metabolites, their redox properties must be conserved. In this study, we have developed a test to measure the electron-donating properties of E2 and its metabolites based on the reduction of Cu(II) ion into Cu(I). Our results show that the catechol- and methoxy-metabolites of E2 lose their capability to reduce Cu(II) into Cu(I) after 3 months of storage at -20 degrees C. Thus, we propose this inexpensive and reliable test to verify the electron-donating properties of E2 metabolites in order to study their ER-independent biological effects in vitro.
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Affiliation(s)
- Paul A Thibodeau
- INSERM U479 Phagocytes et Réponses Inflammatoires, Faculté de Médecine, Université Paris VII Denis Diderot, 16, rue Henri Huchard, Paris 75018, France.
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