ABSTRACT
Carbon tetrachloride [CCl4] is one of the most dangerous hepatotoxic environmental pollutants thus this study aimed at investigating the potential preventive effect and mechanism of crocin against CCl4- induced hepatotoxicity. Forty Male rats were allocated for two weeks treatment with; corn oil, CCl4 in corn oil, crocin [100 mg/kg], or crocin plus CCl4. At time of euthanasia liver was removed, weighted and processed for histopathological evaluation and estimation of liver contents of active caspase3, lipid peroxidation [MDA] and reduced glutathione [GSH]. We also evaluated antioxidant enzymes activities [superoxide dismutase [SOD], glutathione peroxidase [GSH-Px] and catalase [CAT]], phase I metabolizing enzyme [cytochrome P450 sub family 2E1 [CYP2E1]] an Phase II metabolizing enzyme, [glutathione-S-transferase [GST]] in liver tissue. Blood samples were used for evaluation of liver function tests and inflammatory cytokines [interleukin 6 [IL-6] and tumor necrosis factor alpha [TNF-alpha]]. CCl4 induced significant [p < 0.001], increase in: relative liver weight to body weight, liver MDA content, liver active caspase-3 and plasma levels of IL-6 and TNF alpha. In addition, CCl4 disturbed liver histology, liver metabolizing enzymes [CYP2E1 and GST], and liver function tests [aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase]. CCl4 induced significant decrease in activities of SOD, CAT, GSH-Px and GSH content. Administration of crocin with CCl4 mitigated all CCl4-disturbed parameters and preserved liver histology close to normal. Crocin ameliorated CCl4-induced liver injury via inhibition of inflammatory cytokines, caspase3 and oxidative stress along with modulation of liver metabolizing enzymes favoring elimination of CCl4 toxic metabolite