Azzam Shaimaa M, Anwar Hend Mohamed, Abd El-Slam Ahmed H, Diab Marwa S M, Ibrahim Halima Mohamed, Yousef Abdalrahman Mohammed, Sabry Fatma Mahmoud, Darwish Ibrahim A, Kaliyamoorthy Kalidasan, Salem Gad Elsayed Mohamed, Elsanhory Heba M A
Department of Biochemistry, Egyptian Drug Authority (EDA), Formerly National Organization for Drug Control and Research (NODCAR), Giza, Egypt.
Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Front Pharmacol. 2025 Jun 2;16:1551062. doi: 10.3389/fphar.2025.1551062. eCollection 2025.
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 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.
本研究采用生化、组织病理学和免疫组织化学方法，研究了维生素C对利奈唑胺诱导的大鼠肝毒性和肾毒性的保护作用。将24只大鼠分为四组：对照组、利奈唑胺组（100毫克/千克/天）、维生素C组（100毫克/千克/天）以及维生素C与利奈唑胺联合组，给药14天。利奈唑胺治疗导致乳酸性酸中毒，血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、尿素、肌酐和白蛋白水平升高，以及氧化应激，表现为过氧化氢酶活性降低、谷胱甘肽（GSH）减少，同时一氧化氮（NO）和丙二醛（MDA）增加。促炎标志物（白细胞介素-1β、肿瘤坏死因子-α）和肾CD68表达也增加。利奈唑胺破坏自噬（降低Beclin-1水平），并通过无翅/整合（Wnt）信号通路的过度激活诱导细胞凋亡（增加Wnt 7a和Wnt 10a表达）。维生素C治疗通过降低AST、ALT、尿素、肌酐、乳酸、白细胞介素-1β、肿瘤坏死因子-α、NO、MDA和Wnt信号标志物，同时增加白蛋白、过氧化氢酶、GSH和Beclin-1水平，减轻了利奈唑胺的副作用。组织病理学和免疫组织化学分析证实，维生素C与利奈唑胺联合给药的大鼠肝组织和肾组织得到了显著保护。这些结果表明，维生素C可以有效减轻利奈唑胺引起的肝毒性和肾毒性。
