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Protective effect of empagliflozin on gentamicin-induced acute renal injury via regulation of SIRT1/NF-κB signaling pathway
Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2022-06-11 , DOI: 10.1016/j.etap.2022.103907
Sandy R Botros 1 , Asmaa I Matouk 1 , Aliaa Anter 1 , Mohamed M A Khalifa 1 , Gehan H Heeba 1
Affiliation  

Gentamicin is a highly effective antibiotic. However, its major complication is nephrotoxicity. This study investigated the beneficial effects of empagliflozin against gentamicin-induced nephropathy. Kidney damage was induced in male Wistar rats by administration of gentamicin (100 mg/kg/day, i.p.) for 8 days. Two doses of empagliflozin (10 and 20 mg/kg, p.o.) were concomitantly given with gentamicin for 8 days. Gentamicin administration increased serum creatinine, urea, and cystatin C concentrations. Empagliflozin in both doses ameliorated these changes via mitigation of gentamicin-induced increase in renal oxidative stress, inflammation, and apoptosis. Empagliflozin added to GM treatment led to lower measured levels of TGF-B, NF-κB and caspase 3, and only the higher dose increased PAX2 levels indicating an improvement in tubular regeneration. Additionally, empagliflozin (20 mg/kg/day) markedly prevented gentamicin-induced histopathological changes. The protective effects of empagliflozin may be mediated by decreasing gentamicin concentration in renal tissue and possibly other effects like antioxidant and antiapoptotic effects.



中文翻译:

恩格列净通过调节SIRT1/NF-κB信号通路对庆大霉素致急性肾损伤的保护作用

庆大霉素是一种高效抗生素。然而,其主要并发症是肾毒性。本研究调查了恩格列净对庆大霉素诱导的肾病的有益作用通过给予庆大霉素(100 mg/kg/天,ip)8天在雄性Wistar大鼠中诱导肾损伤。两剂 empagliflozin(10 和 20 mg/kg,口服)与庆大霉素同时给药 8 天。庆大霉素给药增加了血清肌酐、尿素和胱抑素 C 浓度。两种剂量的恩格列净通过减轻庆大霉素诱导的肾脏氧化应激、炎症和细胞凋亡增加来改善这些变化。Empagliflozin 添加到 GM 治疗导致 TGF-B、NF-κB 和 caspase 3 的测量水平降低,并且只有较高剂量增加了 PAX2 水平,表明肾小管再生的改善。此外,empagliflozin (20 mg/kg/day) 显着防止庆大霉素诱导的组织病理学变化。

更新日期:2022-06-11
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