Platelet-activating factor (PAF) involvement in acetaminophen-induced liver toxicity and regeneration
| العنوان: | Platelet-activating factor (PAF) involvement in acetaminophen-induced liver toxicity and regeneration |
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| المؤلفون: | Michael G. Mykoniatis, Z. Papadopoulou-Daifoti, A. D. Grypioti, Constantinos A. Demopoulos, A. C. Basayiannis, George K. Papadimas, Stamatios Theocharis |
| المصدر: | Archives of Toxicology. 79:466-474 |
| بيانات النشر: | Springer Science and Business Media LLC, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Thymidine kinase activity, Time Factors, Health, Toxicology and Mutagenesis, Apoptosis, Toxicology, Thymidine Kinase, Pathogenesis, chemistry.chemical_compound, Acetyltransferases, Internal medicine, Mitotic Index, medicine, Animals, Platelet Activating Factor, Rats, Wistar, Acetaminophen, Liver injury, Platelet-activating factor, Liver Diseases, DNA, General Medicine, Analgesics, Non-Narcotic, medicine.disease, Liver regeneration, Liver Regeneration, Rats, medicine.anatomical_structure, Endocrinology, chemistry, Hepatocyte, Toxicity, Hepatocytes, lipids (amino acids, peptides, and proteins), Chemical and Drug Induced Liver Injury, medicine.drug |
| الوصف: | Acetaminophen-induced toxicity has been attributed to cytochrome P-450-generated metabolites, which covalently modify target proteins. However, the mechanism of liver injury pathogenesis needs to be further elucidated. Platelet-activating factor (PAF) is one of the mediators involved in inflammatory tissue alterations associated with acute liver failure. In this study, alterations in blood PAF levels and the serum activity of PAF-acetylhydrolase (PAF-AH) were investigated over the time course of liver injury and regeneration induced by acetaminophen treatment in rats. The administration of a toxic dose of acetaminophen (3.5 g/kg) in rats caused acute hepatic injury, as evident by alterations of biochemical (serum enzymes: ALT, AST and ALP) and liver histopathological (degree of inflammation and apoptosis) indices between 20 and 40 h post-treatment. The hepatic damage was followed by liver regeneration, made evident by three independent indices ([3H]thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index), presenting a peak at 72 h. The PAF levels were elevated at 24 and 28 h, presenting a remarkable peak at 32 h post-treatment. PAF-AH activity presented different kinetics to that of PAF. The enzyme activity was relatively low at all time points examined before the rise in PAF activity, peaking later, at 72, 84 and 96 h. Our data demonstrate that PAF is involved in the pathogenesis of acute liver failure and in augmented compensatory liver tissue repair post-acetaminophen treatment. However, the putative role of PAF during liver toxicity and regeneration remains to be established. |
| تدمد: | 1432-0738 0340-5761 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f107661b0d308d5e0eab30e7a22b4c34 https://doi.org/10.1007/s00204-005-0651-y |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....f107661b0d308d5e0eab30e7a22b4c34 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14320738 03405761 |
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