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Shchegolev AI, Tumanova UN, Savva OV. [Characteristics of structural morphological changes of the liver depending on the prescription of death coming]. Sud Med Ekspert 2023; 66:50-54. [PMID: 36719314 DOI: 10.17116/sudmed20236601150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The purpose of the work is to analyze the literature data devoted to the study of postmortem morphological changes in liver tissue and their use to determine the prescription of death. Postmortem changes are based on the processes of postmortem redistribution of blood and autolysis, the speed and severity of development of which depends primarily on the lifetime pathology, as well as external temperature and humidity during storage of the corpse. The onset of biological death naturally entails the development of postmortem changes in the liver, manifested by a decrease in temperature, violations of the structure of organelles, cells and organ tissue as a whole. The determination and evaluation of developing postmortem morphological changes is necessary both for differential diagnosis with lifetime-developed pathological processes, and for determining the prescription of death coming. This necessitates research to study the features of the development of postmortem changes and to develop ways to assess them to determine the prescription of death coming.
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Affiliation(s)
- A I Shchegolev
- National Medical Research Center of Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov, Moscow, Russia
| | - U N Tumanova
- National Medical Research Center of Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov, Moscow, Russia
| | - O V Savva
- National Medical Research Center of Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov, Moscow, Russia.,D.I. Mastbaum Bureau of Forensic Medical Examination, Ryazan, Russia
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Sefi M, Chaâbane M, Bejaoui S, Elwej A, Marrekchi R, Jamoussi K, Gouiaa N, Sellami TB, El Cafsi M, Zeghal N. Antioxidant role of selenium against maneb-induced cardiotoxicity in mice. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:54827-54841. [PMID: 35312919 DOI: 10.1007/s11356-022-19497-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 02/24/2022] [Indexed: 06/14/2023]
Abstract
The current study was conducted to assess the beneficial effect of selenium (Se) on maneb-induced cardiotoxicity and fatty acid alterations in adult mice. Swiss albino male mice were assigned into four experimental groups. The first group consisted of negative controls. The second group represented the positive controls where mice received daily, via the diet, sodium selenite at a dose of 0.2 mg/kg. For the third group, mice were subjected to intraperitoneal injections of maneb (30 mg/kg BW). The fourth group (MB+Se) received daily the same dose of maneb as group 3 along with sodium selenite at the same dose as group 2. Mice exposure to maneb caused cardiotoxicity as indicated by an increase in malondialdehyde, hydrogen peroxide, and protein carbonyl levels, and an alteration of the antioxidant defense system (catalase, glutathione peroxidase, superoxide dismutase, glutathione, and vitamin C). Plasma lactate dehydrogenase activity and total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels increased, while high-density lipoprotein cholesterol level decreased. Results showed also a decrease in the amount of n-3 PUFA, docosahexaenoic, docosapentaenoic, and eicosapentaenoic acids. However, an increase in the levels of MUFA, cis-vaccenic, and palmitoleic acids was observed. Co-administration of Se restored the parameters indicated above to near control values. The histopathological findings confirmed the biochemical results. Selenium could be a useful and efficient agent against maneb-induced cardiotoxicity.
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Affiliation(s)
- Mediha Sefi
- Animal Physiology Laboratory, Department of Life Sciences, Sciences Faculty of Sfax, University of Sfax, Sfax, Tunisia.
- Ecology, Biology and Physiology Laboratory of Aquatic Organisms, Department of Biological Sciences, Sciences Faculty of Tunis, University of Tunis El Manar, 2092, Tunis, Tunisia.
| | - Mariem Chaâbane
- Animal Physiology Laboratory, Department of Life Sciences, Sciences Faculty of Sfax, University of Sfax, Sfax, Tunisia
| | - Safa Bejaoui
- Ecology, Biology and Physiology Laboratory of Aquatic Organisms, Department of Biological Sciences, Sciences Faculty of Tunis, University of Tunis El Manar, 2092, Tunis, Tunisia
| | - Awatef Elwej
- Animal Physiology Laboratory, Department of Life Sciences, Sciences Faculty of Sfax, University of Sfax, Sfax, Tunisia
| | - Rim Marrekchi
- Biochemistry Laboratory, Department of Biochemistry, CHU Hedi Chaker, University of Sfax, 3029, Sfax, Tunisia
| | - Kamel Jamoussi
- Biochemistry Laboratory, Department of Biochemistry, CHU Hedi Chaker, University of Sfax, 3029, Sfax, Tunisia
| | - Naourez Gouiaa
- Histopathology Laboratory, Department of Anatomo-pathology, CHU Habib Bourguiba, University of Sfax, Sfax, Tunisia
| | - Tahia Boudawara Sellami
- Histopathology Laboratory, Department of Anatomo-pathology, CHU Habib Bourguiba, University of Sfax, Sfax, Tunisia
| | - M'hamed El Cafsi
- Ecology, Biology and Physiology Laboratory of Aquatic Organisms, Department of Biological Sciences, Sciences Faculty of Tunis, University of Tunis El Manar, 2092, Tunis, Tunisia
| | - Najiba Zeghal
- Animal Physiology Laboratory, Department of Life Sciences, Sciences Faculty of Sfax, University of Sfax, Sfax, Tunisia
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Bochimoto H, Ishihara Y, Mohd Zin NK, Iwata H, Kondoh D, Obara H, Matsuno N. Ultrastructural changes in porcine liver sinusoidal endothelial cells of machine perfused liver donated after cardiac death. World J Gastroenterol 2022; 28:2100-2111. [PMID: 35664031 PMCID: PMC9134135 DOI: 10.3748/wjg.v28.i19.2100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 07/17/2021] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The machine perfusion (MP) preservation including hypothermic MP (HMP) and midthermic MP (MMP) has been considered as a promising strategy to preserve the functions of liver donated after cardiac death. The importance of understanding liver sinusoidal endothelial cells (LSEC) damage in regulating liver injury during MP has been emphasized. However, the ultrastructural changes in the LSEC and sinusoids around them after MP are unclear.
AIM To investigate the ultrastructural changes in the LSEC and sinusoids around them after MP.
METHODS Porcine liver grafts undergo a warm ischemia time of 60 minutes perfused for 4 h with modified University of Wisconsin gluconate solution. Group A grafts were preserved with HMP at 8 °C constantly for 4 h. Group B grafts were preserved with a rewarming solution at 22 °C by MMP for 4 h. Then the ultrastructural changes in the LSEC and sinusoids in Group A and B were comparatively analyzed by using osmium-maceration scanning electron microscopy with complementary transmission electron microscopy methods.
RESULTS An analysis of the LSEC after warm ischemia revealed that mitochondria with condensed-shaped cristae, abnormal vesicles, reduction of ribosomes and the endoplasmic reticulum (ER) surround the mitochondria appeared. The MP subsequent after warm ischemia alleviate the abnormal vesicles and reduction of ribosomes in LSEC, which indicated the reduction of the ER damage. However, MMP could restore the tubular mitochondrial cristae, while after HMP the condensed and narrow mitochondrial cristae remained. In addition, the volume of the sinusoidal space in the liver grafts after MMP were restored, which indicated a lower risk of pressure injury than HMP.
CONCLUSION MMP alleviates the ER damage of LSEC by warm ischemia, additionally restore the metabolism of LSEC via the normalization of mitochondria and prevent the share stress damage of liver grafts.
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Affiliation(s)
- Hiroki Bochimoto
- Department of Cell Physiology, The Jikei University School of Medicine, Minato-ku 105-8461, Tokyo, Japan
- Department of Transplantation Technology and Therapeutic Development, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
| | - Yo Ishihara
- Department of Transplantation Technology and Therapeutic Development, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
| | - Nur Khatijah Mohd Zin
- Department of Cell Physiology, The Jikei University School of Medicine, Minato-ku 105-8461, Tokyo, Japan
| | - Hiroyoshi Iwata
- Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
| | - Daisuke Kondoh
- Laboratory of Veterinary Anatomy, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Hokkaido, Japan
| | - Hiromichi Obara
- Department of Transplantation Technology and Therapeutic Development, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
- Department of Mechanical Engineering, Tokyo Metropolitan University, Hachioji 192-0397, Tokyo, Japan
| | - Naoto Matsuno
- Department of Transplantation Technology and Therapeutic Development, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
- Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
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Yadav S, Pawar G, Kulkarni P, Ferris C, Amiji M. CNS Delivery and Anti-Inflammatory Effects of Intranasally Administered Cyclosporine-A in Cationic Nanoformulations. J Pharmacol Exp Ther 2019; 370:843-854. [PMID: 30591529 PMCID: PMC6806630 DOI: 10.1124/jpet.118.254672] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 12/10/2018] [Indexed: 12/12/2022] Open
Abstract
The main objective of this study was to develop and evaluate the CNS delivery efficiency, distribution, therapeutic efficacy, and safety of cyclosporine A (CSA) using a cationic oil-in-water nanoemulsion system upon intranasal administration. An omega-3 fatty acid-rich, flaxseed oil-based nanoemulsion was used for intranasal delivery to the brain, and further magnetic resonance imaging (MRI) was used to evaluate and confirm the transport of the positively charged CSA nanoemulsion (CSA-NE) in CNS. Furthermore, the anti-inflammatory potential of CSA peptide was evaluated using the lipopolysaccharide (LPS) model of neuroinflammation in rats. CSA-NE showed a good safety profile when tested in vitro in RPMI 2650 cells. Upon intranasal administration in rats, the nanoemulsion delivery system showed higher uptake in major regions of the brain based on changes in MRI T1 (longitudinal relaxation time) values. Additionally, CSA nanoemulsion showed improved therapeutic efficacy by inhibiting proinflammatory cytokines in the LPS-stimulated rat model of neuroinflammation compared with solution formulation. Preliminary safety evaluations show that the nanoemulsion system was well tolerated and did not cause any acute negative effects in rats. Based on these results, intranasal delivery of CSA and other "neuroprotective peptides" may provide a clinically translatable strategy for treating neurologic diseases.
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Affiliation(s)
- Sunita Yadav
- Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts (S.Y., G.P., C.F., M.A.); Center for Translational Neuro-Imaging, Northeastern University, Boston, Massachusetts (P.K., C.F.); and Novartis Institute of Biomedical Research, Cambridge, Massachusetts (S.Y.)
| | - Grishma Pawar
- Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts (S.Y., G.P., C.F., M.A.); Center for Translational Neuro-Imaging, Northeastern University, Boston, Massachusetts (P.K., C.F.); and Novartis Institute of Biomedical Research, Cambridge, Massachusetts (S.Y.)
| | - Praveen Kulkarni
- Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts (S.Y., G.P., C.F., M.A.); Center for Translational Neuro-Imaging, Northeastern University, Boston, Massachusetts (P.K., C.F.); and Novartis Institute of Biomedical Research, Cambridge, Massachusetts (S.Y.)
| | - Craig Ferris
- Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts (S.Y., G.P., C.F., M.A.); Center for Translational Neuro-Imaging, Northeastern University, Boston, Massachusetts (P.K., C.F.); and Novartis Institute of Biomedical Research, Cambridge, Massachusetts (S.Y.)
| | - Mansoor Amiji
- Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts (S.Y., G.P., C.F., M.A.); Center for Translational Neuro-Imaging, Northeastern University, Boston, Massachusetts (P.K., C.F.); and Novartis Institute of Biomedical Research, Cambridge, Massachusetts (S.Y.)
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Ahmed A, Alkhawajah AMM, Al-Tamimi DM, Shawarby MA, Isab AA, Badar A. Biological alterations in renal and hepatic tissues by a novel gold (III) anti-cancerous compound. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2018; 21:1064-1072. [PMID: 30524681 PMCID: PMC6281062 DOI: 10.22038/ijbms.2018.28622.6935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Objective(s): Newer organo-metallic, specifically gold (III) complexes with multiple ligands are currently being formulated with primary focus of having increased anti-cancerous properties and decreased cytotoxicity. In this study, histological toxicity profile of a newly formulated anti-cancerous gold (III) compound [trans-(±)-1,2-(DACH)2Au]Cl3 Bis(trans-1,2-Diaminocyclohexane) was investigated by evaluation of kidney and liver tissues of rats treated by the compound. Materials and Methods: This is a quasi-experimental study. In acute toxicity component of the study, (n = 16) male rats weighing between 200–250 g were administered single, variable concentration of the gold (III) compound, [trans-(±)-1,2-(DACH)2Au]Cl3 Bis(trans-1,2-Diaminocyclohexane) to determine LD50 (dose that is lethal to 50% of rats). An IP injection of 2.3 mg/kg (equivalent to 1/10 of LD50) was injected for 14 consecutive days to (n=10) male rats in the sub-acute component of the study. Autopsy preservation of liver and kidney tissue in buffered formalin, sample processing, histopathological evaluation, and comparison with unremarkable controls (n=5) was conducted sequentially. Results: A dose of 2.3 mg/kg did not produce any tubular necrosis in kidney specimens. Mild interstitial inflammation with prominence of plasma cells was the main histological alteration. Plasmacytic pyelitis was also seen. Varying extents of cytoplasmic vacuolization and mild focal lobular and portal inflammation were predominant hepatic microscopic findings. Conclusion: [trans-(±)-1,2-(DACH)2Au]Cl3 Bis(trans-1,2-Diaminocyclohexane) produced no histological damage in renal and hepatic tissues of rats. This very limited sample animal-based study points to the relative safety of this new gold compound. However, there is a need to compare this compound with established drugs in a comparative non-animal based study.
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Affiliation(s)
- Ayesha Ahmed
- Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University and King Fahd Hospital of the University, Dammam, Saudi Arabia
| | | | - Dalal M Al-Tamimi
- Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University and King Fahd Hospital of the University, Dammam, Saudi Arabia
| | - Mohamed A Shawarby
- Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University and King Fahd Hospital of the University, Dammam, Saudi Arabia
| | - Anvarhusein A Isab
- Department of Chemistry, King Fahd University of Petroleum & Minerals, Dhahran, Saudi Arabia
| | - Ahmed Badar
- Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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Bochimoto H, Matsuno N, Ishihara Y, Shonaka T, Koga D, Hira Y, Nishikawa Y, Furukawa H, Watanabe T. The ultrastructural characteristics of porcine hepatocytes donated after cardiac death and preserved with warm machine perfusion preservation. PLoS One 2017; 12:e0186352. [PMID: 29023512 PMCID: PMC5638504 DOI: 10.1371/journal.pone.0186352] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Accepted: 10/01/2017] [Indexed: 12/15/2022] Open
Abstract
The effects of warm machine perfusion preservation of liver grafts donated after cardiac death on the intracellular three-dimensional ultrastructure of the organelles in hepatocytes remain unclear. Here we analyzed comparatively the ultrastructure of the endomembrane systems in porcine hepatocytes under warm ischemia and successive hypothermic and midthermic machine perfusion preservation, a type of the warm machine perfusion. Porcine liver grafts which had a warm ischemia time of 60 minutes were perfused for 4 hours with modified University of Wisconsin gluconate solution. Group A grafts were preserved with hypothermic machine perfusion preservation at 8°C constantly for 4 hours. Group B grafts were preserved with rewarming up to 22°C by warm machine perfusion preservation for 4 hours. An analysis of hepatocytes after 60 minutes of warm ischemia by scanning electron microscope revealed the appearance of abnormal vacuoles and invagination of mitochondria. In the hepatocytes preserved by subsequent hypothermic machine perfusion preservation, strongly swollen mitochondria were observed. In contrast, the warm machine perfusion preservation could preserve the functional appearance of mitochondria in hepatocytes. Furthermore, abundant vacuoles and membranous structures sequestrating cellular organelles like autophagic vacuoles were frequently observed in hepatocytes after warm machine perfusion preservation. In conclusion, the ultrastructure of the endomembrane systems in the hepatocytes of liver grafts changed in accordance with the temperature conditions of machine perfusion preservation. In addition, temperature condition of the machine perfusion preservation may also affect the condition of the hepatic graft attributed to autophagy systems, and consequently alleviate the damage of the hepatocytes.
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Affiliation(s)
- Hiroki Bochimoto
- Health Care Administration Center, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan
| | - Naoto Matsuno
- Department of Surgery, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
- * E-mail:
| | - Yo Ishihara
- Department of Microscopic Anatomy and Cell Biology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Tatsuya Shonaka
- Department of Surgery, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Daisuke Koga
- Department of Microscopic Anatomy and Cell Biology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Yoshiki Hira
- Area of Functional Anatomy, Department of Nursing, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Yuji Nishikawa
- Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Hiroyuki Furukawa
- Department of Surgery, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Tsuyoshi Watanabe
- Department of Microscopic Anatomy and Cell Biology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
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Rowe A, Zhang L, Hussain A, Braet F, Ramzan I. Assessment and histological analysis of the IPRL technique for sequential in situ liver biopsy. COMPARATIVE HEPATOLOGY 2011; 10:7. [PMID: 21819626 PMCID: PMC3199742 DOI: 10.1186/1476-5926-10-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Accepted: 08/08/2011] [Indexed: 11/10/2022]
Abstract
BACKGROUND The isolated perfused rat liver (IPRL) is a technique used in a wide range of liver studies. Typically livers are assessed at treatment end point. Techniques have been described to biopsy liver in the live rat and post-hepatectomy. RESULTS This paper describes a technique for obtaining two full and one partial lobe biopsies from the liver in situ during an IPRL experiment. Our approach of retaining the liver in situ assists in minimising liver capsule damage, and consequent leakage of perfusate, maintains the normal anatomical position of the liver during perfusion and helps to keep the liver warm and moist. Histological results from sequential lobe biopsies in control perfusions show that cytoplasmic vacuolation of hepatocytes is a sign of liver deterioration, and when it occurs it commences as a diffuse pattern which tends to develop a circumscribed, centrilobular pattern as perfusion progresses. CONCLUSIONS Liver lobe biopsies obtained using this method can be used to study temporal effects of drug treatments and are suitable for light and electron microscopy, and biochemical analyses.
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Affiliation(s)
- Anthony Rowe
- Faculty of Pharmacy, University of Sydney, NSW 2006, Australia.
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Thoolen B, Maronpot RR, Harada T, Nyska A, Rousseaux C, Nolte T, Malarkey DE, Kaufmann W, Küttler K, Deschl U, Nakae D, Gregson R, Vinlove MP, Brix AE, Singh B, Belpoggi F, Ward JM. Proliferative and nonproliferative lesions of the rat and mouse hepatobiliary system. Toxicol Pathol 2011; 38:5S-81S. [PMID: 21191096 DOI: 10.1177/0192623310386499] [Citation(s) in RCA: 430] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally-accepted nomenclature for proliferative and non-proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and differential diagnosis for classifying microscopic lesions observed in the hepatobiliary system of laboratory rats and mice, with color microphotographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available for society members electronically on the internet (http://goreni.org). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for lesions of the hepatobiliary system in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.
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Affiliation(s)
- Bob Thoolen
- Global Pathology Support, The Hague, The Netherlands.
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