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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1551062
The Protective Role of Vitamin C against Linezolid Induced Hepato-Renal Toxicity in Rat Model
Provisionally accepted
Shaimaa M Azzam 1 Hend M Anwar 1
Ahmed Altantewy 2 Marwa S M Diab 1 Halima Mohamed Ibrahim 1 Abdalrahman Mohammed Yousef 2
Fatma Sabry 1
Ibrahim Darwish 3
Kalidasan Kaliyamoorthy 4
Gad Elsayed Mohamed Salem 1*
Heba Elsanhory 5- 1 National Organization for Drug Control and Research (NODCAR), Cairo, Cairo, Egypt
- 2 Faculty of Medicine of Boys, Al-Azhar University, Cairo, Beni Suef, Egypt
- 3 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
- 4 Department of Ocean Studies and Marine Biology, Pondicherry University, Port Blair Campus, Port Blair, Puducherry, India
- 5 Sinai University, Cairo, Cairo, Egypt
This study investigated the protective effects of vitamin C against linezolid-induced hepatotoxicity and nephrotoxicity in rats using biochemical, histopathological, and immunohistochemical methods. Twenty-four rats were divided into four groups: control, linezolid (100 mg/kg/day), vitamin C (100 mg/kg/day), and a combination of vitamin C and linezolid for 14 days. Linezolid treatment resulted in lactic acidosis, increased serum levels of AST, ALT, urea, creatinine, and albumin, and oxidative stress characterized by decreased catalase activity and reduced glutathione (GSH) associated with increased nitric oxide (NO) malondialdehyde (MDA). Pro-inflammatory markers (IL-1β, TNF-α) and renal CD68 expression were also increased. Linezolid disrupted autophagy (reduced Beclin-1 levels) and induced apoptosis through hyperactivation of Wingless/integrated (Wnt) signaling (increased Wnt 7a and Wnt 10a expression). Treatment with vitamin C alleviated linezolid side effects by reducing AST, ALT, urea, creatinine, lactic acid, IL-1β, TNF-α, NO, MDA, and Wnt signaling markers while increasing albumin, catalase, GSH, and Beclin-1 levels. Histopathological and immunohistochemical analyses confirmed significant protection of liver and kidney tissues in rats co-administered vitamin C with linezolid. These results suggest that vitamin C can effectively alleviate hepatotoxicity and nephrotoxicity caused by linezolid.
Keywords: linezolid, vitamin C, Hepatotoxicity, nephrotoxicity, Oxidative Stress, Inflammation
Received: 24 Dec 2024; Accepted: 04 Apr 2025.
Copyright: © 2025 Azzam, Anwar, Altantewy, Diab, Ibrahim, Yousef, Sabry, Darwish, Kaliyamoorthy, Salem and Elsanhory. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Gad Elsayed Mohamed Salem, National Organization for Drug Control and Research (NODCAR), Cairo, Cairo, Egypt
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