Abstract
5-fluorouracil (5-FU) is an efficacious fluoropyrimidine antimetabolite anticancer drug, however, its clinical utility is constrained due to side effect toxicity on delicate organs, including the heart. This study thus aimed at exploring the cardioprotective potentials of naringin (NRG) against 5-FU-induced cardiotoxicity in rats. We divided Wistar rats into four experimental groups (n = 6) for the administration of NRG (100 mg/kg bw, orally) and/or 5-FU (150 mg/kg bw, intraperitoneal). NRG was administered for 10 days, while 5-FU was injected on the 8th day only. Serum troponin-I (cTn-I) and creatine kinase (CK) were estimated. Cardiac activities/level of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), malondialdehyde (MDA), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and nuclear factor-ĸB (NF-κB) and caspase-3 were determined. 5-FU markedly increased cTn-I, CK, cardiac inflammatory mediators and caspase-3 expressions, whereas antioxidant mediators decreased appreciably when compared to the control groups. Interestingly, the prophylactic administration of NRG prominently inhibited the 5-FU-provoked oxidative stress, pro-inflammation and apoptosis in the heart of rats. Histopathology confirmed the biochemical results of the heart. Therefore, NRG is a potential natural flavonoid for mitigation of 5-FU cardiotoxicity in rats.
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