الفهرس 
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Abstract
Summary and conclusion br Paracetamol is the most widely used analgesic and antipyretic medication in the world, which has no adverse effect at therapeutic dosages. In high doses, paracetamol causes hepatic necrosis and renal failure in both humans and animals. br Alpha lipoic acid (ALA) is a naturally occurring antioxidant that plays a fundamental role in metabolism. ALA has been shown to affect cellular processes, alter redox status of cells, and interact with thiols and other antioxidants. br The present study is an experimental study. It was performed to: br • Study sub-acute hepatic - renal toxicity of paracetamol. br • Study the possible protective effect of alpha lipoic acid on hepato-renal toxicity of paracetamol. br The study was conducted on 48 adult male healthy albino rats weighing 200 ± 20 g. The ethics and husbandry conditions of animal research were considered according to guide of care and use of laboratory animals approved by the scientific ethics committee of Faculty of Medicine, Sohag University. br The rats were divided randomly into 4 groups, 12 animals each; each -#103;-#114;-#111;-#117;-#112; was subdivided into 2 sub-groups A, B. br • -#103;-#114;-#111;-#117;-#112; I: Gum acacia was administered orally as 2 ml of 2 % suspension orally. -#103;-#114;-#111;-#117;-#112; IA was sacrificed after 4 weeks. -#103;-#114;-#111;-#117;-#112; IB was sacrificed after 8 weeks br • -#103;-#114;-#111;-#117;-#112; II: Alpha lipoic acid was administered orally at the dose of 50 mg /kg body weight/day suspended in 2% gum acacia. -#103;-#114;-#111;-#117;-#112; IIA was sacrificed after 4 weeks while -#103;-#114;-#111;-#117;-#112; IIB was sacrificed after 8 weeks. br • -#103;-#114;-#111;-#117;-#112; III: Paracetamol was administered orally at a dose of 1 g/kg body weight /day suspended in 2% gum acacia for 4 weeks. br -#103;-#114;-#111;-#117;-#112; IIIA was sacrificed after 4 weeks. br -#103;-#114;-#111;-#117;-#112; IIIB was left without treatment for another 4weeks and sacrificed. br • -#103;-#114;-#111;-#117;-#112; IV: br -#103;-#114;-#111;-#117;-#112; IVA was treated with paracetamol and ALA (the same previous doses) for 4 weeks then sacrificed. -#103;-#114;-#111;-#117;-#112; IVB was treated with paracetamol and ALA(the same previous doses) for 4weeks, then treated with ALA only for another 4weeks then sacrificed. br Biochemical results: br Results of liver functions tests: br • Serum level of ALT and AST, in animal groups that ingested toxic dose of paracetamol with or without ALA, was higher than normal. br • Co-administration of ALA with toxic dose of paracetamol could not prevent the increase of serum level of ALT and AST, but the rise was less severe. br • Improvement in liver biochemistry occurred after a period of recovery for 4 weeks following ingestion of toxic dose of paracetamol, despite that it did not return to normal values as control groups. br • While in -#103;-#114;-#111;-#117;-#112; IVB, treatment with ALA for 4 weeks after stoppage of paracetamol showed improvement of serum level of ALT and AST up to return to normal level as control. br • There was a significant statistical decrease in serum total protein induced by toxic dose of paracetamol which did not occur0when0paracetamol0was0co-administered0with0ALA. The0decline0in0serum0total0protein0improved0after.period.of.recovery.for.4.weeks. br br Results of kidney functions tests: br • Serum urea level showed a significant statistical increase with toxic dose of paracetamol and lesser increase when ALA was co-administered with paracetamol. br • Improvement of serum urea level occurred after period of recovery for 4 weeks. While, better improvement followed similar period of treatment with ALA. br • The paracetamol treated -#103;-#114;-#111;-#117;-#112; showed an elevation in creatinine level. This renal dysfunction improved by administration of ALA. Lesser improvement in the serum creatinine level occurred after a period of spontaneous recovery without ALA. br Results of oxidative stress markers br • Administration of paracetamol induced significant decrease in superoxide dismutase (SOD) and catalase (CAT) activities and elicited a significant increase in malondialdhyde (MDA) level as compared to control group. br • There was an ameliorative role of ALA when co-administered with toxic dose of paracetamol (-#103;-#114;-#111;-#117;-#112; IVA). Better results were achieved when ALA was administered after stoppage of paracetamol (-#103;-#114;-#111;-#117;-#112; IVB). br Histopathological results of the study groups: br Liver histo-pathological results. br • Many histo-pathological changes were observed in paracetamol treated -#103;-#114;-#111;-#117;-#112; (-#103;-#114;-#111;-#117;-#112; IIIA) in the form of marked dilatation and congestion of central veins and portal venules. Also, there was marked vacuolar degeneration of hepatocytes. br • The severity of the hepatic changes decreased when paracetamol was co-adminstered with alpha lipoic acid (-#103;-#114;-#111;-#117;-#112; IVA) and after a period of recovery following paracetamol administration (-#103;-#114;-#111;-#117;-#112; IIIB). br • Further improvement occurred when ALA was administered after stoppage of paracetamol (-#103;-#114;-#111;-#117;-#112; IVB) in the form of mild dilatation and congestion of central vein and portal venules. Also, there was mild vacuolar degeneration of hepatocytes. br Kidney histopathological results br • Histo-pathological examination of kidney -#102;-#114;-#111;-#109; paracetamol only -#103;-#114;-#111;-#117;-#112; revealed marked hydropic degeneration of renal tubules. While, there was moderate hydropic degeneration of renal tubules and moderate dilated congested blood vessels in paracetamol withdrawal -#103;-#114;-#111;-#117;-#112; (-#103;-#114;-#111;-#117;-#112; IIIB) and paracetamol and ALA -#103;-#114;-#111;-#117;-#112; (-#103;-#114;-#111;-#117;-#112; IVA). br • Further improvement occurred in the treatment -#103;-#114;-#111;-#117;-#112; (-#103;-#114;-#111;-#117;-#112; IVB) in the form of mild hydropic degeneration of renal tubules. br Conclusion br • It has been found that repeated oral administration of paracetamol affects liver and kidney both functionally and pathologically. Also, oxidative stress has occurred in the form of increased level of MDA and decreased level of SOD and catalase. br • Alpha lipoic acid has the ability to protect against hepatotoxicity, nephrotoxicity and oxidative stress induced by paracetamol.