Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey.
Department of Physiology, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey.
Pharmacol Res Perspect. 2024 Aug;12(4):e1222. doi: 10.1002/prp2.1222.
Gentamicin is an aminoglycoside antibiotic with a rapid bactericidal effect on the treatment of many infections. However, its use at high concentrations for more than 7 days causes nephrotoxic side effects. This study investigated the potential of Resatorvid and alpha lipoic acid (ALA) in mitigating gentamicin-induced nephrotoxicity in rats, considering biochemical, histopathological, and molecular parameters. This study randomly distributed 34 Wistar albino rats into four groups: healthy control (n = 6), Gentamicin (80 mg/kg, n = 7), Gentamicin + Sham (%10 hydroalcoholic solution, n = 7), Gentamicin + Resatorvid (5 mg/kg, n = 7), and Gentamicin + ALA (100 mg/kg, n = 7). Resatorvid treatment led to a statistically significant decrease in urinary IL-18, KIM-1, and NGAL levels, whereas ALA treatment significantly reduced KIM-1 levels compared to the gentamicin-only group. Both Resatorvid and ALA showed partial reductions in urine creatinine levels. Moreover, treatments with Resatorvid and ALA resulted in statistically significant decreases in NRF-2, CAS-3, and NR4A2 expressions. However, only Resatorvid demonstrated a statistically significant decrease in NF-B expression. These findings highlight the potential of Resatorvid in ameliorating gentamicin-induced nephrotoxicity, thereby expanding the therapeutic utility of gentamicin and enhancing its efficacy against infections.
庆大霉素是一种氨基糖苷类抗生素,对许多感染具有快速杀菌作用。然而,高浓度使用超过 7 天会导致肾毒性副作用。本研究探讨了雷沙吉兰和α-硫辛酸(ALA)在减轻大鼠庆大霉素诱导的肾毒性中的潜力,考虑了生化、组织病理学和分子参数。本研究将 34 只 Wistar 白化大鼠随机分为四组:健康对照组(n=6)、庆大霉素组(80mg/kg,n=7)、庆大霉素+假处理组(10%水醇溶液,n=7)、庆大霉素+雷沙吉兰组(5mg/kg,n=7)和庆大霉素+ALA 组(100mg/kg,n=7)。雷沙吉兰治疗导致尿白细胞介素-18(IL-18)、肾损伤分子-1(KIM-1)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平显著降低,而与仅用庆大霉素组相比,ALA 治疗显著降低了 KIM-1 水平。雷沙吉兰和 ALA 治疗均使尿肌酐水平部分降低。此外,雷沙吉兰和 ALA 治疗导致核因子红细胞 2(NRF-2)、半胱氨酸天冬氨酸蛋白酶 3(CAS-3)和核受体亚家族 4 组 A 成员 2(NR4A2)表达显著降低。然而,只有雷沙吉兰显示核因子-κB(NF-κB)表达显著降低。这些发现强调了雷沙吉兰在减轻庆大霉素诱导的肾毒性方面的潜力,从而扩大了庆大霉素的治疗用途,并提高了其对抗感染的疗效。