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

Lipopolysaccharide (LPS) is the major cell wall component of gram-negative bacteria known to stimulate the synthesis and secretion of several toxic metabolites, such as reactive oxygen species and cytokines. In this study, the protective effect of alpha-lipoic acid (ALA) and coenzyme Q10 (CoQ10) were evaluated in LPS-induced hepatic injury in rats. To this end, male adult Sprague Dawley rats were divided into five groups; normal control, LPS control where rats were injected with an initial dose of LPS (4 mg/kg; i.p.) on the 1stday of the experiment followed by a challenging dose (2 mg/kg; i.p.) on the 8th day, ALA (50 mg/kg), CoQ10 (10 mg/kg) and ALA plus CoQ10. Treatments continued for 15 days and the last three groups also received LPS. At the end of the study, liver function tests, as well as interleukin-6 (IL-6) were estimated in serum. Liver lipid peroxides measured as malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total antioxidant capacity (TAC) were also assessed, in addition to histological examination of liver sections from all groups. The obtained data revealed that LPS markedly elevated activities of serum aminotransferases, alkaline phosphatase and gamma-glutamyl transferase, as well as, total bilirubin and interleukin-6 levels. LPS-treated rats showed an increase in MDA liver content versus decrease in GSH content, SOD activity and TAC. Oral administration of ALA, CoQ10 and their combination ameliorated LPS-induced increases in liver function enzymes and IL-6, coupled by hampering of oxidative biomarkers. This was also supported by histopathological evaluation results. In conclusion, administration of ALA, CoQ10 and their combination improved pathological abnormalities in liver tissues and reversed the deleterious effects induced by LPS

Issued also as CD