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

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

Cardiovascular & hematological disorders drug targets - 23(2023), 3 vom: 09., Seite 189-201

Sprache:

Englisch

Beteiligte Personen:

Gadekar, Gayatri Jaising [VerfasserIn]
Bhandare, Pranali Anandrao [VerfasserIn]
Bandawane, Deepti Dinesh [VerfasserIn]

Links:

Volltext

Themen:

268B43MJ25
5-FU
76845O8NMZ
8W8T17847W
AYI8EX34EU
Acacia catechu
Antioxidant enzymes.
Antioxidants
Biomarkers
Catalase
Creatinine
EC 1.11.1.6
EC 1.15.1.1
Ethyl acetate
Fluorouracil
Journal Article
Nephroprotective
Nephrotoxicity
Renal biomarkers
Superoxide Dismutase
TNF-α
Tumor Necrosis Factor-alpha
U3P01618RT
Urea
Uric Acid

Anmerkungen:

Date Completed 03.01.2024

Date Revised 20.03.2024

published: Print

Citation Status MEDLINE

doi:

10.2174/011871529X274030231102065433

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM364380209