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McSweeney KR, Gadanec LK, Kubatka P, Caprnda M, Gaspar L, Prosecky R, Delev D, Kruzliak P, Apostolopoulos V, Zulli A. Cisplatin treatment reduces contraction to angiotensin II by altering expression of angiotensin II receptors: a pilot study. Mol Cell Biochem 2023; 478:2907-2916. [PMID: 37004639 DOI: 10.1007/s11010-023-04706-2] [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: 12/04/2022] [Accepted: 03/10/2023] [Indexed: 04/04/2023]
Abstract
The renin angiotensin system is a key regulator of blood pressure homeostasis. Angiotensin type 1 (AT1R) and 2 receptors (AT2R) have been investigated as targets for cisplatin-induced acute kidney injury; however, their therapeutic potential remains inconclusive. This pilot study aimed to determined the effect that acute cisplatin treatment had on angiotensin II (AngII)-induced contraction in blood vessels and expression profiles of AT1R and AT2R in mouse arteries and kidneys. Male C57BL/6 mice at 18 week of age (n = 8) were treated with vehicle or bolus dose of cisplatin (12.5 mg/kg). Thoracic aorta (TA), adnominal aorta (AA), brachiocephalic arteries (BC), iliac arteries (IL) and kidneys were collected for isometric tension and immunohistochemistry analysis. Cisplatin treatment reduced IL contraction to AngII at all doses (p < 0.01, p < 0.001, p < 0.0001); however, AngII did not induce contraction in TA, AA or BC in either treatment group. Following cisplatin treatment, AT1R expression was significantly upregulated in the media of TA (p < 0.0001) and AA (p < 0.0001), and in the endothelium (p < 0.05) media (p < 0.0001) and adventitia (p < 0.01) of IL. Cisplatin treatment significantly reduced AT2R expression in the endothelium (p < 0.05) and media (p < 0.05) of TA. In renal tubules, both AT1R (p < 0.01) and AT2R (p < 0.05) were increased following cisplatin treatment. Herein, we report that cisplatin reduces AngII-mediated contraction in IL and may be explained by an absence of normal counterregulatory expression of AT1R and AT2R, indicating other factors are involved.
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Affiliation(s)
| | - Laura Kate Gadanec
- Institute of Health and Sport, Victoria University, Melbourne, Vic, Australia
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Martin Caprnda
- 1st Department of Internal Medicine, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia
| | - Ludovit Gaspar
- Faculty of Health Sciences, University of Ss. Cyril and Methodius in Trnava, Trnava, Slovakia
| | - Robert Prosecky
- 2nd Department of Internal Medicine, Faculty of Medicine, Masaryk University and St. Anne's University Hospital, Brno, Czech Republic
- International Clinical Research Centre, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic
| | - Delian Delev
- Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria
| | - Peter Kruzliak
- 2nd Department of Surgery, Faculty of Medicine, Masaryk University and St. Anne's University Hospital, Brno, Czech Republic.
| | - Vasso Apostolopoulos
- Institute of Health and Sport, Victoria University, Melbourne, Vic, Australia
- Australian Institute for Musculoskeletal Science (AIMSS), Melbourne, VIC, Australia
| | - Anthony Zulli
- Institute of Health and Sport, Victoria University, Melbourne, Vic, Australia.
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2
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Nemmar A, Beegam S, Zaaba NE, Elzaki O, Pathan A, Ali BH. Waterpipe smoke inhalation induces lung injury and aortic endothelial dysfunction in mice. Physiol Res 2023; 72:337-347. [PMID: 37449747 PMCID: PMC10669000 DOI: 10.33549/physiolres.935042] [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: 11/28/2022] [Accepted: 02/28/2023] [Indexed: 08/26/2023] Open
Abstract
Waterpipe tobacco smoking (WPS) inhalation has been shown to trigger endothelial dysfunction and atherosclerosis. However, the mechanisms underlying these effects are still unknown. Here, we assessed the impact and underlying mechanism of WPS exposure for one month on endothelial dysfunction using aortic tissue of mice. The duration of the session was 30 min/day and 5 days/week. Control mice were exposed to air. Inhalation of WPS induced an increase in the number of macrophages and neutrophils and the concentrations of protein, tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1beta, and glutathione in bronchoalveolar lavage fluid. Moreover, the concentrations of proinflammatory cytokines (TNF alpha, IL-6 and IL-1beta), adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin and P-selectin) and markers of oxidative stress (lipid peroxidation, glutathione, superoxide dismutase and nitric oxide) in aortic homogenates of mice exposed to WPS were significantly augmented compared with air exposed mice. Likewise, the concentration of galectin-3 was significantly increased in the aortic homogenates of mice exposed to WPS compared with control group. WPS inhalation induced vascular DNA damage assessed by comet assay and apoptosis characterized by a significant increase in cleaved caspase-3. While the aortic expression of phosphorylated nuclear factor kappaB (NF-kappaB) was significantly increased following WPS inhalation, the concentration of sirtuin 1 (SIRT1) was significantly decreased in WPS group compared with air-exposed group. In conclusion, our study provided evidence that WPS inhalation triggers lung injury and endothelial inflammation, oxidative stress and apoptosis which were associated with nuclear factor-kappaB activation and SIRT1 down-regulation.
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Affiliation(s)
- A Nemmar
- Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. and
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3
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Uruski P, Matuszewska J, Leśniewska A, Rychlewski D, Niklas A, Mikuła-Pietrasik J, Tykarski A, Książek K. An integrative review of nonobvious puzzles of cellular and molecular cardiooncology. Cell Mol Biol Lett 2023; 28:44. [PMID: 37221467 DOI: 10.1186/s11658-023-00451-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 04/17/2023] [Indexed: 05/25/2023] Open
Abstract
Oncologic patients are subjected to four major treatment types: surgery, radiotherapy, chemotherapy, and immunotherapy. All nonsurgical forms of cancer management are known to potentially violate the structural and functional integrity of the cardiovascular system. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical subdiscipline, called cardiooncology. This relatively new, but rapidly expanding area of knowledge, primarily focuses on clinical observations linking the adverse effects of cancer therapy with deteriorated quality of life of cancer survivors and their increased morbidity and mortality. Cellular and molecular determinants of these relations are far less understood, mainly because of several unsolved paths and contradicting findings in the literature. In this article, we provide a comprehensive view of the cellular and molecular etiology of cardiooncology. We pay particular attention to various intracellular processes that arise in cardiomyocytes, vascular endothelial cells, and smooth muscle cells treated in experimentally-controlled conditions in vitro and in vivo with ionizing radiation and drugs representing diverse modes of anti-cancer activity.
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Affiliation(s)
- Paweł Uruski
- Department of Hypertensiology, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Julia Matuszewska
- Department of Pathophysiology of Ageing and Civilization Diseases, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Aleksandra Leśniewska
- Department of Pathophysiology of Ageing and Civilization Diseases, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Daniel Rychlewski
- Department of Pathophysiology of Ageing and Civilization Diseases, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Arkadiusz Niklas
- Department of Hypertensiology, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Justyna Mikuła-Pietrasik
- Department of Pathophysiology of Ageing and Civilization Diseases, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Andrzej Tykarski
- Department of Hypertensiology, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Krzysztof Książek
- Department of Pathophysiology of Ageing and Civilization Diseases, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland.
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4
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Yang HM, Hou TZ, Zhang YN, Zhao SD, Wu YL, Zhang H. Blocked metabotropic glutamate receptor 5 enhances chemosensitivity in hepatocellular carcinoma and attenuates chemotoxicity in the normal liver by regulating DNA damage. Cancer Gene Ther 2022; 29:1487-1501. [PMID: 35396501 DOI: 10.1038/s41417-022-00465-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 03/08/2022] [Accepted: 03/21/2022] [Indexed: 12/12/2022]
Abstract
DNA damaging agents are used as chemotherapeutics in many cancers, including hepatocellular carcinoma (HCC). However, they are associated with problems such as low sensitivity to chemotherapy and the induction of liver injury, underscoring the need to identify new therapies. Here, we investigated the differential regulatory effect of metabotropic glutamate receptor 5 (mGlu5) on chemosensitivity in HCC and chemotoxicity to the normal liver. The expression of mGlu5 was higher in HCC than in the normal liver, and correlated with poor prognosis according to The Cancer Genome Atlas database and Integrative Molecular Database of Hepatocellular Carcinoma. Cisplatin, oxaliplatin or methyl methanesulfonate (MMS) caused cell death by decreasing mGlu5 expression in HCC cells and increased mGlu5 expression in hepatic cells. In HCC cells, inhibition of mGlu5 aggravated MMS-induced DNA damage by increasing intracellular Ca2+ overload and mitogen-activated protein kinase (MAPK) activation, thereby promoting cell death, and activation of mGlu5 rescued the effect of MMS. However, in hepatic cells, mGlu5 inhibition alleviated MMS-induced DNA damage by downregulating Ca2+-derived MAPK pathways to advance hepatic cell survival. The opposite effects of mGlu5 overexpression or knockdown on MMS-induced DNA damage supported that cell death is a result of the differential regulation of mGlu5 expression. Inhibition of mGlu5 increased chemosensitivity and decreased chemotoxicity in a rat tumor model. This study suggests that mGlu5 inhibition could act synergistically with HCC chemotherapeutics with minimal side effects, which may improve the treatment of patients with HCC in the future.
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Affiliation(s)
- Hui-Min Yang
- Department of Neurobiology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Capital Medical University, 100069, Beijing, China
| | - Tian-Zhong Hou
- Department of Neurobiology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Capital Medical University, 100069, Beijing, China
| | - Ya-Nan Zhang
- Department of Neurobiology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Capital Medical University, 100069, Beijing, China
| | - Shu-Dong Zhao
- Department of Neurobiology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Capital Medical University, 100069, Beijing, China
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Engineering Medicine, Beihang University, 100083, Beijing, China
| | - Yong-Le Wu
- Center of Hepatic and Digestive Disease, Beijing YouAn Hospital, Capital Medical University, 100069, Beijing, China
| | - Hong Zhang
- Department of Neurobiology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Capital Medical University, 100069, Beijing, China.
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Scafa-Udriste A, Popa-Fotea NM, Bataila V, Calmac L, Dorobantu M. Acute inferior myocardial infarction in a young man with testicular seminoma: A case report. World J Clin Cases 2021; 9:4040-4045. [PMID: 34141764 PMCID: PMC8180225 DOI: 10.12998/wjcc.v9.i16.4040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 01/29/2021] [Accepted: 03/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Atherosclerosis represents the main cause of myocardial infarction (MI); other causes such as coronary embolism, vasospasm, coronary-dissection or drug use are much rarely encountered, but should be considered in less common clinical scenarios. In young individuals without cardiovascular risk factors, the identification of the cause of MI can sometimes be found in the medical history and previous treatments undertaken.
CASE SUMMARY We present the case of a 34-year-old man presenting acute inferior ST-elevation MI without classic cardiac risk factors. Seven years ago, he suffered from orchidopexy for bilateral cryptorchidism, and was recently diagnosed with right testicular seminoma for which he had to undergo surgical resection and chemotherapy with bleomycin, etoposide and cisplatin. Shortly after the first chemotherapy treatment, namely on day five, he suffered an acute MI. Angiography revealed a mild stenotic lesion at the level of the right coronary artery with suprajacent thrombus and vasospasm, with no other significant lesions on the other coronary arteries. A conservative treatment was decided upon by the cardiac team, including dual antiplatelets therapy and anticoagulants with good further evolution. The patient continued the chemotherapy treatment according to the initial plan without other cardiovascular events.
CONCLUSION In young individuals with no cardiovascular risk factors undergoing aggressive chemotherapy, an acute MI can be caused by vascular toxicity of several anti-cancer drugs.
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Affiliation(s)
- Alexandru Scafa-Udriste
- Department of Cardio-Thoracic, University of Medicine and Pharmacy, Bucharest 050474, Romania
- Department of Cardiology, Emergency Clinical Hospital, Bucharest 014461, Romania
| | - Nicoleta-Monica Popa-Fotea
- Department of Cardio-Thoracic, University of Medicine and Pharmacy, Bucharest 050474, Romania
- Department of Cardiology, Emergency Clinical Hospital, Bucharest 014461, Romania
| | - Vlad Bataila
- Department of Cardiology, Emergency Clinical Hospital, Bucharest 014461, Romania
| | - Lucian Calmac
- Department of Cardiology, Emergency Clinical Hospital, Bucharest 014461, Romania
| | - Maria Dorobantu
- Department of Cardio-Thoracic, University of Medicine and Pharmacy, Bucharest 050474, Romania
- Department of Cardiology, Emergency Clinical Hospital, Bucharest 014461, Romania
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Gene regulatory network analysis with drug sensitivity reveals synergistic effects of combinatory chemotherapy in gastric cancer. Sci Rep 2020; 10:3932. [PMID: 32127608 PMCID: PMC7054272 DOI: 10.1038/s41598-020-61016-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 02/19/2020] [Indexed: 12/14/2022] Open
Abstract
The combination of docetaxel, cisplatin, and fluorouracil (DCF) is highly synergistic in advanced gastric cancer. We aimed to explain these synergistic effects at the molecular level. Thus, we constructed a weighted correlation network using the differentially expressed genes between Stage I and IV gastric cancer based on The Cancer Genome Atlas (TCGA), and three modules were derived. Next, we investigated the correlation between the eigengene of the expression of the gene network modules and the chemotherapeutic drug response to DCF from the Genomics of Drug Sensitivity in Cancer (GDSC) database. The three modules were associated with functions related to cell migration, angiogenesis, and the immune response. The eigengenes of the three modules had a high correlation with DCF (−0.41, −0.40, and −0.15). The eigengenes of the three modules tended to increase as the stage increased. Advanced gastric cancer was affected by the interaction the among modules with three functions, namely cell migration, angiogenesis, and the immune response, all of which are related to metastasis. The weighted correlation network analysis model proved the complementary effects of DCF at the molecular level and thus, could be used as a unique methodology to determine the optimal combination of chemotherapy drugs for patients with gastric cancer.
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7
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Nemmar A, Al-Salam S, Beegam S, Yuvaraju P, Ali BH. Aortic Oxidative Stress, Inflammation and DNA Damage Following Pulmonary Exposure to Cerium Oxide Nanoparticles in a Rat Model of Vascular Injury. Biomolecules 2019; 9:biom9080376. [PMID: 31426470 PMCID: PMC6722935 DOI: 10.3390/biom9080376] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 07/28/2019] [Accepted: 07/29/2019] [Indexed: 12/21/2022] Open
Abstract
Pulmonary exposure to cerium oxide nanoparticles (CeO2 NPs) can occur either at the workplace, or due to their release in the environment. Inhaled CeO2 NPs are known to cross the alveolar–capillary barrier and reach various parts of the body, including the vasculature. The anticancer drug cisplatin (CP) causes vascular damage. However, the effects CeO2 NPs on vascular homeostasis in a rat model of CP-induced vascular injury remain unclear. Here, we assessed the impact and underlying mechanism of pulmonary exposure to CeO2 NPs on aorta in rats given a single intraperitoneal injection of cisplatin (CP, 6 mg/kg) to induce vascular damage. Six days later, the rats were intratracheally instilled with either CeO2 NPs (1 mg/kg) or saline (control), and various variables were studied 24 h thereafter in the aortic tissue. The concentration of reduced glutathione and the activity of catalase were significantly increased in the CP + CeO2 NPs group compared with both the CP + saline and the CeO2 NPs groups. The activity of superoxide dismutase was significantly decreased in the CP + CeO2 NPs group compared with both the CP + saline and CeO2 NPs groups. The expression of nuclear factor erythroid-derived 2-like 2 (Nrf2) by the nuclei of smooth muscles and endocardial cells assessed by immunohistochemistry was significantly augmented in CeO2 NPs versus saline, in CP + saline versus saline, and in CP + CeO2 NPs versus CeO2 NPs. Moreover, the concentrations of total nitric oxide, lipid peroxidation and 8-hydroxy-2-deoxyguanosine were significantly elevated in the CP + CeO2 NPs group compared with both the CP + saline and the CeO2 NPs groups. Similarly, compared with both the CP + saline and CeO2 NPs groups, the combination of CP and CeO2 NPs significantly elevated the concentrations of interleukin-6 and tumour necrosis factor-α. Additionally, aortic DNA damage assessed by Comet assay was significantly increased in CeO2 NPs compared with saline, and in CP + saline versus saline, and all these effects were significantly aggravated by the combination of CP and CeO2 NPs. We conclude that pulmonary exposure to CeO2 NPs aggravates vascular toxicity in animal model of vascular injury through mechanisms involving oxidative stress, Nrf2 expression, inflammation and DNA damage.
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Affiliation(s)
- Abderrahim Nemmar
- Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE
- Correspondence:
| | - Suhail Al-Salam
- Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE
| | - Sumaya Beegam
- Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE
| | - Priya Yuvaraju
- Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE
| | - Badreldin H. Ali
- Department of Pharmacology, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 35, Muscat 123, Al-Khoud, Oman
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Williams MRM, Bertrand B, Hughes DL, Waller ZAE, Schmidt C, Ott I, O'Connell M, Searcey M, Bochmann M. Cyclometallated Au(iii) dithiocarbamate complexes: synthesis, anticancer evaluation and mechanistic studies. Metallomics 2019; 10:1655-1666. [PMID: 30255182 DOI: 10.1039/c8mt00225h] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
A series of cationic mixed cyclometallated (C^N)Au(iii) dithiocarbamate complexes has been synthesized in good yields [HC^N = 2-(p-t-butylphenyl)pyridine]. The crystal structure of [(C^N)AuS2CNEt2]PF6 (3) has been determined. The cytotoxic properties of the new complexes have been evaluated in vitro against a panel of human cancer cell lines and healthy cells and compared with a neutral mixed (C^C)Au(iii) dithiocarbamate complex (C^C = 4,4'-di-t-butylbiphenyl-2,2'-diyl). The complexes appeared to be susceptible to reduction by glutathione but were stable in the presence of N-acetyl cysteine. The potential mechanism of action of this class of compounds has been investigated by measuring the intracellular uptake of some selected complexes, by determining their interactions with higher order DNA structures, and by assessing the ability to inhibit thioredoxin reductase. The complexes proved unable to induce the formation of reactive oxygen species. The investigations add to the picture of the possible mode of action of this class of complexes.
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Herradón E, González C, Uranga JA, Abalo R, Martín MI, López-Miranda V. Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments. Front Pharmacol 2017; 8:196. [PMID: 28533750 PMCID: PMC5420557 DOI: 10.3389/fphar.2017.00196] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Accepted: 03/24/2017] [Indexed: 01/17/2023] Open
Abstract
In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.
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Affiliation(s)
- Esperanza Herradón
- Área de Histología Humana y Anatomía Patológica, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan CarlosAlcorcón, Spain.,Unidad Asociada ICDCi del Instituto de Química Médica, Consejo Superior de Investigaciones CientíficasMadrid, Spain.,Grupo Interdisciplinar de Investigación en Dolor iCDol, Universidad Rey Juan Carlos-Banco de SantanderAlcorcón, Spain
| | - Cristina González
- Área de Histología Humana y Anatomía Patológica, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan CarlosAlcorcón, Spain.,Unidad Asociada ICDCi del Instituto de Química Médica, Consejo Superior de Investigaciones CientíficasMadrid, Spain.,Grupo Interdisciplinar de Investigación en Dolor iCDol, Universidad Rey Juan Carlos-Banco de SantanderAlcorcón, Spain
| | - José A Uranga
- Grupo Interdisciplinar de Investigación en Dolor iCDol, Universidad Rey Juan Carlos-Banco de SantanderAlcorcón, Spain.,Área de Histología Humana y Anatomía Patológica, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan CarlosAlcorcón, Spain
| | - Raquel Abalo
- Área de Histología Humana y Anatomía Patológica, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan CarlosAlcorcón, Spain.,Unidad Asociada ICDCi del Instituto de Química Médica, Consejo Superior de Investigaciones CientíficasMadrid, Spain.,Grupo Interdisciplinar de Investigación en Dolor iCDol, Universidad Rey Juan Carlos-Banco de SantanderAlcorcón, Spain
| | - Ma I Martín
- Área de Histología Humana y Anatomía Patológica, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan CarlosAlcorcón, Spain.,Unidad Asociada ICDCi del Instituto de Química Médica, Consejo Superior de Investigaciones CientíficasMadrid, Spain.,Grupo Interdisciplinar de Investigación en Dolor iCDol, Universidad Rey Juan Carlos-Banco de SantanderAlcorcón, Spain
| | - Visitacion López-Miranda
- Área de Histología Humana y Anatomía Patológica, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan CarlosAlcorcón, Spain.,Unidad Asociada ICDCi del Instituto de Química Médica, Consejo Superior de Investigaciones CientíficasMadrid, Spain.,Grupo Interdisciplinar de Investigación en Dolor iCDol, Universidad Rey Juan Carlos-Banco de SantanderAlcorcón, Spain
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