Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats

Background: Methotrexate (MTX) is used commonly in the treatment of various cancers and inflammatory diseases; nevertheless, the associated hepatotoxicity has limited its clinical application. Crocin (CRO) is described as a natural carotenoid with analgesic, antioxidant, and antiinflammatory properties. This study aimed to determine the effects of CRO on MTX-induced hepatotoxicity. Methods: For pretreatment, CRO at doses of 25 and 50 mg/kg (po), as well as 20 mg/kg (ip) of MTX, was injected in rats. Results: MTX led to hepatotoxicity, as confirmed by the significant increase in liver markers, histopathological changes, decreased GSH content, and reduced antioxidant enzyme activity (i.e., CAT, SOD, and GPx). It increased TNF-alpha, IL-1 beta, lipid peroxidation, and nitric oxide levels. Nevertheless, by increasing antioxidant defense in hepatic tissues and reducing oxidative stress and proinflammatory mediators, pretreatment with CRO could alleviate hepatotoxicity. Conclusion: CRO can inhibit MTX-induced hepatotoxicity through improving antioxidant defense and reducing oxidative stress and inflammation. (C) 2019 Maj Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.