Prophylactic administration of naringin prevents anticancer drug 5-fluorouracil-induced hepatorenal toxicity via suppressing lipid peroxidation and oxidative stress in rats

Abstract

Background

5-fluorouracil (5-FU)-based anticancer chemotherapy is widely used in many solid tumours; however, hepatorenal toxicity is a serious side effect associated with its clinical use. Therefore, the current study investigated the potential of a natural flavonoid, naringin (NRG), for possible prevention of 5-FU hepatorenal toxicity in rats.

Method

Rats were divided into four groups (n = 6): Control, NRG, 5-FU, and NRG + 5-FU. Accordingly, rats were orally administered NRG (100 mg/kg bodyweight/day) for 10 days, while 5-FU (150 mg/kg bw/day) was intraperitoneally injected on day 8 only. On the 11th day, rats were sacrificed for collection of blood samples, liver and kidney organs for biochemical and histological analyses.

Results

5-FU injection induced significant (p < 0.05) increases in activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and levels of uric acid, creatinine, urea, and malondialdehyde. It was observed that 5-FU considerably (p < 0.05) reduced the antioxidant activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione (GSH) level. The histopathological abrasions revealed tissue damage consistent with oxidative stress-mediated injury. Interestingly, the prophylactic administration of NRG significantly (p < 0.05) prevented the 5-FU-induced alterations in the hepatorenal markers and maintained the antioxidant status comparable to the control. The NRG dose also ameliorated the oxidative tissue damage in this study.

Conclusion

It is evident from the findings that NRG may prevent 5-FU-induced oxidative hepatorenal injury in rats.