Protective Effects of Crocetin against Thioacetamide-induced Liver Fibrosis in Rats

Background: Liver fibrosis represents irreversible liver destruction. Crocetin, a carotenoid dicarboxylic acid found in saffron, possesses anti-inflammatory, antioxidant and anti-apoptotic properties. This study investigated crocetin’s hepatoprotective effects against thioacetamide-induced liver fibrosis in rats, focusing on its potential therapeutic mechanisms. Methods: Forty male Wistar albino rats were divided into four groups: control (normal saline), crocetin (40 mg/kg, i.p.), thioacetamide (200 mg/kg, i.p., twice weekly for 6 weeks) and thioacetamide+crocetin (pretreatment with crocetin before thioacetamide). Various biochemical and histological parameters were assessed. Result: Thioacetamide administration increased oxidative stress markers (nitric oxide, malondialdehyde), decreased antioxidants, elevated inflammatory markers (IL-1b, TNF-a, NF-kB) and impaired liver enzymes. Histologically, it caused cirrhotic nodules and extensive necrosis. Crocetin treatment restored antioxidant levels, reduced lipid peroxidation, suppressed inflammatory cytokines, regulated the Bax/Bcl-2 ratio and normalized liver enzyme levels. The protective effects of crocetin were particularly evident in liver tissue morphology, where it significantly prevented the formation of fibrotic bridges, maintained hepatocyte integrity and preserved sinusoidal structure. Additionally, biochemical analysis revealed that crocetin treatment effectively restored glutathione peroxidase and catalase activities to near-normal levels. The study concluded that crocetin effectively mitigates thioacetamide-induced hepatic fibrosis through its antioxidative, anti-inflammatory and anti-apoptotic properties, suggesting potential therapeutic applications in liver disease.