| Title | Expression of VEGF isoforms in rats after the induction of liver injury and regeneration with a toxic dose of paracetamol | |
| Authors | Vasilios P. Papastefanou¹, Evangelos Bozas³, Stavros Garifallidis⁴, Polyxeni Nikolopoulou² and Michael G. Mykoniatis¹
Departments of 1. Experimental Pharmacology and 2. Pathology, Medical School, National and Kapodistrian University of Athens 3. Pediatric Research Laboratory, Faculty of Nursing, National and Kapodistrian Univesity of Athens 4. Patision General Hospital, Athens, Greece |
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| Citation | Papastefanou, V.P., Bozas, E., Garifallidis S., Nikolopoulou, P., Mykoniatis, M.G.: Expression of VEGF isoforms in rats after the induction of liver injury and regeneration with a toxic dose of paracetamol, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 292-295 (2006) | |
| Publication Date | Accepted for publication: 19-20 May 2006 | |
| Full Text Language | English | |
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| Keywords | Paracetamol, hepatotoxicity, VEGF, angiogenesis, liver regeneration. | |
| Other Terms | review article | |
| Summary | VEGF is a potent angiogenetic and vascular permeability factor that has been associated with liver regeneration post partial hepatectomy and hepatotoxicity. Paracetamol is a widely used over the counter analgesic that has been proved to be hepatotoxic upon overdosage. The aim of this study is to examine the expression of VEGF isoforms after the induction of liver injury and regeneration with an acute dosage of paracetamol in rats. A toxic dose of paracetamol (3.5 glkg b.w.) was administered per os to adult male Sprague Dawley rats. The rats were sacrificed upon regular time intervals spanning a range of 0-288 hours. The liver was excised and blood was drawn from the heart of each animal. The blood samples were used for the evaluation of AST, ALT and ALP. The extent of the hepatic damage was evaluated with the use of hematoxylin and eosin tissue specimens. The m-RNA expression of isoforms VEGF188, VEGF165, VEGF144 and VEGF120 were examined with semi-quantitative reverse- transcriptase PCR. Paracetamol induced extensive tissue damage as indicated from the levels of the hepatic enzymes peaking at 24-48 hrs post administration. Interestingly, both AST and ALT peaked again at 192 hrs post administration. The pathologic examination demonstrated the development of centrilobular necrosis at 24-36 hrs post administration and the gradual restoration of the hepatic microarchitecture from 72 hours to 288 hours post administration. The isoforms of VEGF had a varying expression over time with a common finding – three peaks of expression at 12hrs, 72hrs and 192 hrs post administration. In conclusion, paracetamol is, as proved in the past and in this study, a potent hepatotoxic factor upon overdosage. VEGF, on the other hand, does play an active role in acetaminophen-induced liver injury and regeneration. The three peak expression of all isoforms during the time span examined observed is another indicator of the many aspects of liver regeneration that remain yet to be elucidated. | |
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Online ISSN 1011-6575
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Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
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