Evaluation of the protective effect of taurine, seleno l-methionine and l-carnitine against acetaminophen-induced hepatotoxicity in rats / Nermeen Elsaeed Mansour Elsharkawy ; Supervised Ezz Eldin Eldenshary , Hala Fahmy Zaki , Wafaa Eleraky

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacologya and Toxicology

Background: Paracetamol (APAP) is a commonly used analgesic and antipyretic. Toxic doses of APAP, however, cause massive hepatocellular apoptosis and necrosis. Taurine (TAU) is an essential amino acid that possesses a number of cytoprotective properties through its actions as an antioxidant, anti-apoptotic and intracellular calcium flux regulator. Seleno L-methionine (Se-met) it is source of selenium (Se) that increases the activity of glutathione peroxidase. The major antioxidant role of glutathione peroxidase in liver cells is to maintain appropriately low levels of hydrogen peroxides via glutathione reductase and convert it to water, thus decreasing potential free radical damage. L-carnitine (CAR) is a mitochondria-specific antioxidant that plays an important role in oxidative/antioxidative balance by scavenging reactive oxygen species and increasing ATP production. Aim of the study: The present work was designed to examine the possible protective effects of TAU, Se-met and CAR against APAP -induced liver injury. Method: Male Wistar rats were allocated into eight groups of 10 animals each. Group I received saline p.o. for 7 days (normal group), group II received TAU (200 mg/kg; p.o.) for 7 days , group III received Se-met (0.4 mg/kg; p.o.) for 7 days , group IV received CAR (300 mg/kg; p.o.) for 7 days, group V received saline for 7 days followed by a single dose of APAP (700 mg/kg; p.o.) on the 8th day (APAP control group), group VI received TAU (200 mg/kg; p.o.) .) for 7 days followed by APAP, group VII received Se-met (0.4 mg/kg; p.o.) .) for 7 days followed by APAP and group VIII received CAR (300 mg/kg; p.o.) for 7 days followed by APAP on the 8th day group. Rats were sacrificed 24 h thereafter. Parameters used to assess the protective effect of TAU, Se-met and CAR included serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities as well as liver contents of thiobarbituric acid reactive substances, reduced glutathione, nitric oxide, total antioxidant capacity, tumor necrosis factor-alpha and transforming growth factor- beta in addition to histological examination of liver sections from all studied groups

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