EVALUATION OF THE SYNERGISTIC PROTECTIVE EFFECTS OF VITAMIN C, N-ACETYLCYSTEINE, AND SODIUM FERULATE ON INFLAMMATION, OXIDATIVE STRESS, AND NEPHROTOXICITY IN 5-FLUOROURACIL-TREATED RATS

Eldib, Ali M.; Mufti, Rania E.; Babikir, Ibrahim H.; El-Gerbed, Mohamed S.; Khalifa, Heba S.; El-Anwar, Noha; Abdelatif, Haytham M.

doi:10.21608/ejz.2025.375371.1130

	EVALUATION OF THE SYNERGISTIC PROTECTIVE EFFECTS OF VITAMIN C, N-ACETYLCYSTEINE, AND SODIUM FERULATE ON INFLAMMATION, OXIDATIVE STRESS, AND NEPHROTOXICITY IN 5-FLUOROURACIL-TREATED RATS
Egyptian Journal of Zoology
Articles in Press, Accepted Manuscript, Available Online from 18 May 2025 PDF (1.15 MB)
Document Type: Original Research Papers
DOI: 10.21608/ejz.2025.375371.1130
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Authors
Ali M. Eldib ¹; Rania E. Mufti²; Ibrahim H. Babikir²; Mohamed S. El-Gerbed¹; Heba S. Khalifa¹; Noha El-Anwar²^{, 3}; Haytham M. Abdelatif²^{, 4}
¹Zoology Department, Faculty of Science, Damanhour University, Damanhour, Egypt
²Basic Science Department, Al Rayan National College of Medicine, Al-Madinah Al-Munawwarah, Saudi Arabia
³Pathology Department, Faculty of Medicine, Tanta University, Gharbia, Egypt
⁴Pharmacology Department, Faculty of Medicine, Sohag University, Sohag, Egypt
Abstract
The current research aimed to assess the protective effects of a mixture of natural products (N.P.), containing vitamin C, N-acetylcysteine (NAC), and sodium ferulate, against 5-fluorouracil (5-FU)-induced inflammation, nephrotoxicity, and oxidative stress in rats. Forty male rats were divided into four groups: a control group (G1), a N.P. mix-treated group given daily/orally (G2), a 5-FU-treated group administered intraperitoneal injections of 15 mg/kg body weight for 4 consecutive days, 6 mg/kg body weight for 4 alternative days, and 15 mg/kg body weight on day 14 (G3), and a group treated with 5-FU+N.P. mix (G4). The 5-FU treatment induced severe changes in immunity and biochemical parameters like elevated serum creatinine and urea levels, and disturbed electrolyte balance (P<0.05). Oxidative stress in the kidneys was also extremely high, as reflected by enhanced malondialdehyde and nitric oxide, and suppressed the antioxidants (SOD, CAT, GSH). The proinflammatory cytokines (IL-1β, IL-6, TNF-α, INF-γ) and complements were also significantly upregulated, while anti-inflammatory (IL-10, TGF-β) and T-cell functional cytokines (IL-2, IL-4, IL-12) were significantly suppressed. Moreover, the histological examination showed massive renal tubular necrosis and glomerular atrophy. The immunohistochemistry also revealed overexpression of proapoptotic markers; while flow cytometry determined increased apoptosis and depletion of CD3⁺CD4⁺T-helper lymphocytes. In contrast, co-treatment with 5-FU+N.P. mix substantially alleviated these pathological changes. It normalized biochemical parameters, reduced oxidative stress, improved antioxidant status, suppressed proinflammatory cytokines, and preserved renal histoarchitecture and T-cell numbers (P<0.05). These findings may validate the efficacy of the used N.P. mix as a nephroprotective, immune-modulating adjuvant in chemotherapy.
Keywords
5-Fluorouracil; Immunomodulation; Natural products; Oxidative stress; Renal apoptosis


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