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 AzzamShaimaa M Azzam1Hend M AnwarHend M Anwar1Ahmed AltantewyAhmed Altantewy2Marwa S M DiabMarwa S M Diab1Halima Mohamed IbrahimHalima Mohamed Ibrahim1Abdalrahman Mohammed YousefAbdalrahman Mohammed Yousef2Fatma SabryFatma Sabry1Ibrahim DarwishIbrahim Darwish3Kalidasan KaliyamoorthyKalidasan Kaliyamoorthy4Gad Elsayed Mohamed SalemGad Elsayed Mohamed Salem1*Heba ElsanhoryHeba Elsanhory5
  • 1National Organization for Drug Control and Research (NODCAR), Cairo, Cairo, Egypt
  • 2Faculty of Medicine of Boys, Al-Azhar University, Cairo, Beni Suef, Egypt
  • 3Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
  • 4Department of Ocean Studies and Marine Biology, Pondicherry University, Port Blair Campus, Port Blair, Puducherry, India
  • 5Sinai University, Cairo, Cairo, Egypt

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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

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material