Crocin Alleviates 5-Fluorouracil-induced Hepatotoxicity through the abrogation of Oxidative Stress in Male Wistar rats

Abstract

5-Fluorouracil (5-FU) is a pyrimidine analogue that is used as an anti-cancer drug but its therapeutic potential is limited by its hepatotoxicity. This study therefore, aimed at investigating the protective effect of crocin, a natural supplement, against 5-FU-induced liver injury. Male rats were administered with 5-FU (30 mg/kg b.wt i.p.) for 5 days. Two groups of animals were either orally treated 3 days prior to or 3 days after 5-FU administration with crocin (40 mg/kg bwt). Another group was concurrently treated with crocin along with 5-FU administration. Biochemical variables indicative of liver injury, oxidative stress and liver histopathological alterations were thereafter determined. 5-FU administration markedly increased oxidative stress and markers of hepatic injury. Pre-, concurrent and post-treatment with crocin significantly reduced MDA, AOPP and LOOH levels and increased total antioxidant capacity compared to the 5-FU alone group, with improvement in the activities of the antioxidant enzymes, SOD, CAT and PONase. Liver injury was markedly reversed when AST, ALT and ALP activities estimated in the three treatment groups were compared to 5-FU group, but the restoration was incomplete, compared to the control. These biochemical variables were supported by histopathological examinations. The results indicate that crocin supplementation can ameliorate 5-FU-induced oxidative stress and liver injury in rat.