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雷沙吉兰和硫辛酸对庆大霉素致大鼠肾毒性的潜在影响。

Potential effects of Resatorvid and alpha lipoic acid on gentamicin-induced nephrotoxicity in rats.

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey.

Department of Physiology, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey.

出版信息

Pharmacol Res Perspect. 2024 Aug;12(4):e1222. doi: 10.1002/prp2.1222.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2975/11239954/01871c171797/PRP2-12-e1222-g001.jpg

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