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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro
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No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro

机译：依帕格列净和达格列净对糖尿病患者体外肾原发性肾小管上皮细胞无细胞毒性和炎症作用

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摘要

Gliflozins are inhibitors of the renal proximal tubular sodium-glucose co-transporter-2 (SGLT-2), that inhibit reabsorption of urinary glucose and they are able to reduce hyperglycemia in patients with type 2 diabetes. A renoprotective function of gliflozins has been proven in diabetic nephropathy, but harmful side effects on the kidney have also been described. In the current project, primary highly purified human renal proximal tubular epithelial cells (PTCs) have been shown to express functional SGLT-2, and were used as an in vitro model to study possible cellular damage induced by two therapeutically used gliflozins: empagliflozin and dapagliflozin. Cell viability, proliferation, and cytotoxicity assays revealed that neither empagliflozin nor dapagliflozin induce effects in PTCs cultured in a hyperglycemic environment, or in co-medication with ramipril or hydro-chloro-thiazide. Oxidative stress was significantly lowered by dapagliflozin but not by empagliflozin. No effect of either inhibitor could be detected on mRNA and protein expression of the pro-inflammatory cytokine interleukin-6 and the renal injury markers KIM-1 and NGAL. In conclusion, empa- and dapagliflozin in therapeutic concentrations were shown to induce no direct cell injury in cultured primary renal PTCs in hyperglycemic conditions.
机译：格列净是肾脏近端肾小管钠-葡萄糖共转运蛋白2（SGLT-2）的抑制剂，可抑制尿糖的重吸收，并且能够减少2型糖尿病患者的高血糖症。在糖尿病肾病中已经证明了格列净的肾保护功能，但是也已经描述了对肾脏的有害副作用。在当前项目中，已显示高纯度原代人肾近端肾小管上皮细胞（PTC）可表达功能性SGLT-2，并用作体外模型，以研究由两种治疗性使用的格列净诱导的可能细胞损伤：依格列净和达格列净。细胞活力，增殖和细胞毒性试验表明，依帕列净和达格列净均不诱导在高血糖环境中或与雷米普利或氢氯噻嗪联合用药的PTC中产生作用。达格列净可显着降低氧化应激，但依帕格列净则无明显降低。没有检测到任何一种抑制剂对促炎细胞因子白细胞介素6和肾损伤标记物KIM-1和NGAL的mRNA和蛋白表达的影响。总之，在高血糖情况下，治疗浓度的Empa- dapagliflozin和dapagliflozin均不会在培养的原发性肾PTC中引起直接细胞损伤。

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