Amelioration of 5-Fluorouracil Induced Nephrotoxicity by Acacia catechu through Overcoming Oxidative Damage and Inflammation in Wistar Rats.

AIM: The research intended to explore the possible nephroprotective potential of the ethyl acetate fraction derived from Acacia catechu leaves against nephrotoxicity brought about by 5-fluorouracil (5-FU) in Wistar rats. BACKGROUND: While possessing strong anticancer properties, 5-FU is hindered in its therapeutic application due to significant organ toxicity linked to elevated oxidative stress and inflammation. OBJECTIVE: The study is undertaken to conduct an analysis of the ethyl acetate fraction of A. catechu leaves both in terms of quality and quantity, examining its impact on different biochemical and histopathological parameters within the context of 5-FU-induced renal damage in rats and elucidation of the mechanism behind the observed outcomes. METHODOLOGY: Intraperitoneal injection of 5-FU at a dosage of 20 mg/kg/day over 5 days was given to induce nephrotoxicity in rats. The evaluation of nephrotoxicity involved quantifying serum creatinine, urea, uric acid, and electrolyte concentrations. Furthermore, superoxide dismutase, catalase antioxidant enzymes, and TNF-α concentration in serum were also measured. RESULTS: 5-FU injection led to the initiation of oxidative stress within the kidneys, leading to modifications in renal biomarkers (including serum creatinine, urea, uric acid, and Na+, K+ levels), and a reduction in antioxidant enzymes namely superoxide dismutase and catalase. Notably, the presence of the inflammatory cytokine TNF-α was significantly elevated due to 5-FU. Microscopic examination of renal tissue revealed tubular degeneration and congestion. However, treatment involving the ethyl acetate fraction derived from A. catechu leaves effectively and dose-dependently reversed the changes observed in renal biomarkers, renal antioxidant enzymes, inflammatory mediators, and histopathological features, bringing them closer to normal conditions. The observed recuperative impact was mainly attributed to the antioxidant and antiinflammatory properties of the fraction. CONCLUSION: The ethyl acetate fraction of A. catechu leaves exhibited a mitigating influence on the renal impairment caused by 5-FU, showcasing its potential as a nephroprotective agent capable of preventing and ameliorating 5-FU-induced nephrotoxicity.

Hepatoprotective Activity of Gentisic Acid on 5-Fluorouracil-induced Hepatotoxicity in Wistar Rats

Objectives: 5-Fluorouracil (5-FU) is a very potent and effective antineoplastic drug that has been widely used for the management of various types of cancer. However, the clinical use of 5-FU is often associated with severe toxicities including hepatotoxicity, which limit its therapeutic use as a potent anticancer agent. The present study aimed to evaluate the hepatoprotective activity of a plant phenolic acid, gentisic acid (GA) (2,5-dihyroxybenzoic acid), against hepatotoxicity induced by 5-FU administration in Wistar rats. Materials and Methods: The rats were randomly divided into six groups, with six rats per group. Among these, group I and II served as normal control and 5-FU control groups, respectively. The rats in these groups received distilled water (1 mL/kg) for 14 days by oral route. Groups III, IV, V, and VI served as test groups and received GA at doses of 3, 10, 30, and 100 mg/kg body weight, respectively, via oral route for 14 days. From Day 9 onwards, all the groups, except group I, received intraperitoneal dose of 5-FU (20 mg/kg body weight) for five days up to day 14. At the end of the study, the rats were sacrificed, blood was withdrawn for biochemical estimations, and hepatic tissues were excised for histopathological evaluations. Results: Administration of 5-FU at a dose of 20 mg/kg body weight resulted in a significant increase in the serum levels of hepatic biomarkers, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct bilirubin, and total bilirubin. In comparison to these, 5-FU treatment resulted in a reduction in total protein content (TPC). This was accompanied by significant histopathological changes in the hepatic tissues of the rats, indicating severe hepatotoxicity. Pre- and co-administration of GA with 5-FU at doses of 30 and 100 mg/kg body weight for 14 days resulted in a dose-dependent amelioration of the 5-FU induced alterations in the biochemical and histopathological parameters. Conclusion: The results of the study highlighted the potential of GA as a hepatoprotective agent for the prevention of 5-FU-induced hepatotoxicity.