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

Hepatotoxicity is one of the most frequent adverse events occurring due to the extensive exposure of the liver to high concentrations of xenobiotics. Gender and sex hormones are known to play a role in the bioavailability, metabolism and lethality of many toxic substances. This study was conducted to investigate the influence of sex hormones in both; male and female rats on D-galactosamine and lipopolysaccharide (D-GalN/LPS)- induced hepatotoxicity in comparison to alpha-lipoic acid (Ü-LA). Male and female rats were treated with Ü-LA (100 mg/kg, orally), estradiol for female rats (15 og /kg, s.c.) and testosterone for male rats (2.5 mg/kg, i.m.) for 14 consecutive days. One hour after the last treatment, induction of hepatotoxicity by injection of GalN (300 mg/kg, i.p.) and LPS (30 og/ kg, i.p.) was carried out. Twenty-four hours later, animals were sacrificed. Blood and liver samples were collected to assess serum tumor necrosis factor-alpha (TNF-{uF061}) level, activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) enzymes. Liver samples were histopathologically assessed, reduced glutathione (GSH) and malondialdehyde (MDA) contents in liver homogenate were determined. Testosterone significantly decreased serum ALT, AST, ALP and TNF-Ü levels, it also significantly increased GSH and decreased MDA contents in liver homogenate as compared to D-GalN/LPS treated male rats. Moreover, estrogen significantly decreased serum AST, ALP and TNF-Ü levels but there was no significant difference on serum ALT or GSH and MDA contents in liver homogenate as compared to D-GalN/LPS treated female rats. These results suggest that pretreatment with sex hormones prior to administration of D-GalN/LPS can provide protection against hepatotoxicity in male and female rats, while Ü-lipoic acid restored various cellular activities which emphasize the antioxidant potential of lipoic acid in ameliorating the hepatotoxicity

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