Crocin mitigates carbon tetrachloride-induced liver toxicity in rats

AbstractObjectivesCarbon 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.MethodsForty Male rats were allocated for two weeks treatment with; corn oil, CCl4 in corn oil, crocin (100mg/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-α)].ResultsCCl4 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-α. 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.ConclusionCrocin 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