The Protective Effects of Alpha-Tocopherol Against Gentamicin-Induced Nephrotoxicity: The Potential Role of the Nrf۲/NQO۱ Pathway

Introduction: Aminoglycosides like gentamicin can cause nephrotoxicity by increasing reactive oxygen species (ROS) and reducing antioxidants. The transcription factor Nrf۲ regulates antioxidant genes like NQO۱ to combat oxidative stress. This study evaluated Nrf۲/NQO۱ involvement in gentamicin renal toxicity and vitamin E protection.Materials and Methods: ۲۴ rats were divided into control, gentamicin, vitamin E, and gentamicin plus vitamin E groups. Gentamicin (۱۰۰ mg/kg) and vitamin E (۲۵۰ mg/kg) were given intraperitoneally for ۸ days. Kidney function, oxidative stress, Nrf۲/NQO۱ expression, and histology were analyzed.Results: Gentamicin significantly increased serum creatinine by ۱.۹۸-fold (۱.۴۳ ± ۰.۴۹ vs ۰.۷۲ ± ۰.۱۶ mg/dl, p <۰.۰۱) and BUN by ۵.۵۸-fold (۲۵۲.۳ ± ۷۸.۱۳ vs ۴۵.۱۸ ± ۷.۲۶ mg/dl, p <۰.۰۰۰۱) compared to control. Gentamicin also markedly suppressed renal Nrf۲ mRNA expression by ۸۳% and NQO۱ by ۷۹% versus control (p <۰.۰۰۰۱). Vitamin E partially alleviated the functional impairment and downregulation of Nrf۲ and NQO۱ caused by gentamicin. The vitamin E group displayed the highest Nrf۲ (۲.۸-fold vs control) and NQO۱ (۱.۶-fold vs control) expression among all groups (p <۰.۰۰۰۱).Conclusions: Gentamicin appears to cause nephrotoxicity partly by suppressing Nrf۲/NQO۱ antioxidant defense. Vitamin E provided renoprotection by scavenging ROS and potentially reactivating Nrf۲/NQO۱. The study suggests oxidative stress is an important mechanism in aminoglycoside kidney toxicity that may be mitigated by appropriate antioxidants. Evaluating Nrf۲/NQO۱ modulation provides insights into gentamicin nephrotoxicity and related kidney injuries.

کلیدواژه ها:

Acute Kidney Injury ، ، Gentamicin ، α-Tocopherol ، ، Nrf۲ ، ، NQO۱