Eldib, A., Mufti, R., Babikir, I., El-Gerbed, M., Khalifa, H., El-Anwar, N., Abdelatif, H. (2025). 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, (), -. doi: 10.21608/ejz.2025.375371.1130
Ali M. Eldib; Rania E. Mufti; Ibrahim H. Babikir; Mohamed S. El-Gerbed; Heba S. Khalifa; Noha El-Anwar; Haytham M. Abdelatif. "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, , , 2025, -. doi: 10.21608/ejz.2025.375371.1130
Eldib, A., Mufti, R., Babikir, I., El-Gerbed, M., Khalifa, H., El-Anwar, N., Abdelatif, H. (2025). '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, (), pp. -. doi: 10.21608/ejz.2025.375371.1130
Eldib, A., Mufti, R., Babikir, I., El-Gerbed, M., Khalifa, H., El-Anwar, N., Abdelatif, H. 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, 2025; (): -. 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
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.