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

Protective effect of empagliflozin on gentamicin-induced acute renal injury via regulation of SIRT1/NF-κB signaling pathway.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt.

出版信息

Environ Toxicol Pharmacol. 2022 Aug;94:103907. doi: 10.1016/j.etap.2022.103907. Epub 2022 Jun 11.

DOI:10.1016/j.etap.2022.103907
PMID:35697188
Abstract

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.

摘要

庆大霉素是一种高效的抗生素。然而,其主要并发症是肾毒性。本研究探讨了恩格列净对庆大霉素诱导的肾病的有益作用。通过腹腔注射庆大霉素(100mg/kg/天)8 天,诱导雄性 Wistar 大鼠的肾脏损伤。同时给予恩格列净(10 和 20mg/kg,po)两种剂量 8 天。庆大霉素给药增加了血清肌酐、尿素和胱抑素 C 的浓度。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,改善了这些变化。在 GM 治疗中添加恩格列净导致 TGF-β、NF-κB 和 caspase 3 的测量水平降低,只有高剂量增加了 PAX2 水平,表明肾小管再生得到改善。此外,恩格列净(20mg/kg/天)显著预防了庆大霉素引起的组织病理学变化。恩格列净的保护作用可能是通过降低肾组织中的庆大霉素浓度和可能的其他作用如抗氧化和抗细胞凋亡作用来介导的。

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