Ameliorative Effect of Naringenin in 5-Fluorouracil-Induced Hepatotoxicity: An Experimental Study on Albino Wistar Rats

Abstract

Background: Hepatotoxicity is an adverse complication in 5-Fluorouracil cancer treatment. Inflammation, oxidative stress, apoptosis and DNA damage are essential in the pathogenesis of liver damage. The present study evaluated the ameliorative effect of Naringenin (NG) in 5-FU at two different intervals in hepatic damage. Methods: Total (n=48) Albino Wistar rats were divided into 4 groups (N=12), Control-normal saline (group-1) per oral, 5-FU (group-2) @ 20 mg/kg b.wt was injected intraperitoneal (IP) for first 5 days, NG (group-3) @100 mg/kg b. wt/day orally for 28 days. Another group-4 was concurrently treated with NG along with 5-FU for 28 days and sacrificed on the 14th and 28th day of the experiment. Result: On exposure to 5-FU, biochemical variation of liver enzymes (ALT, AST, ALP and TP) were significantly increased while NG treatment significantly reduced these biomarkers in group 2 on 14th day and 28th day of the experiment. Furthermore, NG treatment significantly reduced lipid peroxidation and increases the antioxidant profile. It also significantly reduced elevated concentrations of pro-inflammatory cytokines like tumour necrosis factor (TNF-α), interleukin -1β (IL-1β), interleukin-6 (IL-6) with increased concentrations of interleukin-10 (IL-10) along with reduced immunohistochemical expression of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and Caspases -3 (Cas-3) by NG. On histopathology, pathological lesions were observed to support biochemical variations in group-2 rats. In group-4 rats, NG ameliorates liver enzymes, inflammatory cytokines and oxidative indices through an anti-oxidant, anti-inflammatory and anti-apoptotic property.