Abd Elmaaboud Maaly A, Kabel Ahmed M, Elrashidy Mohamed
Tanta University, Faculty of Medicine, Department of Pharmacology, Tanta, Egypt.
Taif University, College of Pharmacy, Department of Clinical Pharmacy, Taif, Saudi Arabia.
J Appl Biomed. 2019 Mar;17(1):90. doi: 10.32725/jab.2019.003. Epub 2019 Feb 6.
Dose-limiting nephrotoxicity restricts Cisplatin use in high therapeutic doses. Empagliflozin showed a reno-protective effect in diabetic nephropathy. We investigated if Empagliflozin can ameliorate Cisplatin nephrotoxicity whether used prophylactically or therapeutically. Forty male Wistar rats were divided into 5 groups: (1) control; (2) Cisplatin-induced nephrotoxicity by single intraperitoneal dose; (3) Empagliflozin was given for 10 days before a single dose of Cisplatin; (4) a single dose of Cisplatin followed by Empagliflozin for 10 days; (5) received Empagliflozin only. Regular assessment of weight was done, biochemical evaluation for serum urea, creatinine, uric acid, albumin, and glucose was performed, kidney tissue nerve growth factor-β (NGF-β) and oxidative stress parameters were measured, kidneys were evaluated histopathologically and immunostained for caspase 3. Cisplatin significantly reduced body weight, NGF-β, and reduced glutathione, elevated urea, creatinine, and malondialdehyde with no effect on other serum biochemical parameters. Histopathologically, there was high acute tubular necrosis (ATN) score with strong immunostaining of caspase 3. The use of Empagliflozin significantly reduced urea and creatinine in both prophylactic and therapeutic, reduced ATN score in the prophylactic group associated with minimal staining of caspase 3 and elevated reduced glutathione. In conclusion, prophylactic Empagliflozin protected against Cisplatin-induced acute kidney injury mainly via anti-apoptotic effect.
剂量限制性肾毒性限制了顺铂在高治疗剂量下的使用。恩格列净在糖尿病肾病中显示出肾脏保护作用。我们研究了恩格列净无论预防性还是治疗性使用，是否都能改善顺铂肾毒性。40只雄性Wistar大鼠分为5组：(1)对照组；(2)单次腹腔注射顺铂诱导肾毒性组；(3)在单次注射顺铂前给予恩格列净10天组；(4)单次注射顺铂后给予恩格列净10天组；(5)仅接受恩格列净组。定期评估体重，进行血清尿素、肌酐、尿酸、白蛋白和葡萄糖的生化评估，测量肾组织神经生长因子-β(NGF-β)和氧化应激参数，对肾脏进行组织病理学评估并对caspase 3进行免疫染色。顺铂显著降低体重、NGF-β和还原型谷胱甘肽，升高尿素、肌酐和丙二醛，对其他血清生化参数无影响。组织病理学上，急性肾小管坏死(ATN)评分高，caspase 3免疫染色强。恩格列净的使用在预防性和治疗性使用中均显著降低尿素和肌酐，在预防性组中降低ATN评分，伴有caspase 3的最小染色，并升高还原型谷胱甘肽。总之，预防性使用恩格列净主要通过抗凋亡作用预防顺铂诱导的急性肾损伤。
