Title:Amelioration of 5-Fluorouracil Induced Nephrotoxicity by Acacia catechu
through Overcoming Oxidative Damage and Inflammation in Wistar Rats
Volume: 23
Issue: 3
Author(s): Gayatri Jaising Gadekar, Pranali Anandrao Bhandare and Deepti Dinesh Bandawane*
Affiliation:
- Department of Pharmacology, P. E. Society’s Modern College of Pharmacy, Nigdi, Pune- 44, India
Keywords:
5-FU, Acacia catechu, nephroprotective, nephrotoxicity, TNF-α, renal biomarkers, antioxidant enzymes.
Abstract:
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.