Becerir Tülay, Tokgün Onur, İnci Kubilay, Girişgen İlknur, Yuksel Selcuk
Department of Pediatric Nephrology, Pamukkale University School of Medicine, Denizli, TUR.
Department of Medical Genetics, Pamukkale University School of Medicine, Denizli, TUR.
Cureus. 2022 Apr 6;14(4):e23871. doi: 10.7759/cureus.23871. eCollection 2022 Apr.
Background Drug-induced nephrotoxicity is an important side effect of many commonly used drugs. In this study, we planned to evaluate the effects of teneligliptin (TG), which is a dipeptidyl peptidase-4 (DPP-4) inhibitor, on cell healing by creating nephrotoxicity models in human renal proximal tubule cell and human embryonic kidney epithelial cells cell lines in-vitro with cisplatin, vancomycin, and gentamicin. Methodology First, we determined the 50% inhibitory concentration doses of nephrotoxic drugs and the nephroprotective dose of TG. Then, we analyzed the difference in cell viability, apoptosis, and oxidative stress (reactive oxygen and nitrogen species (ROS/RNS) production) between TG-treated and untreated cells after nephrotoxicity occurred. Moreover, we evaluated the expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in cells. Results We found that when cell lines were treated after toxicity was induced with TG, cell viability increased, apoptosis and ROS/RNS production were significantly decreased, and expressions of KIM-1 and NGAL were significantly reduced. Conclusions This study showed that TG has positive effects on the recovery of drug-induced nephrotoxicity in an in-vitro setting.
背景 药物性肾毒性是许多常用药物的重要副作用。在本研究中，我们计划通过用顺铂、万古霉素和庆大霉素在体外建立人肾近端小管细胞和人胚肾上皮细胞系的肾毒性模型，来评估二肽基肽酶-4（DPP-4）抑制剂替格列汀（TG）对细胞修复的影响。
方法 首先，我们确定了肾毒性药物的50%抑制浓度剂量和TG的肾保护剂量。然后，我们分析了肾毒性发生后TG处理组和未处理组细胞在细胞活力、凋亡和氧化应激（活性氧和氮物种（ROS/RNS）产生）方面的差异。此外，我们评估了细胞中肾损伤分子-1（KIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的表达。
结果 我们发现，在用TG诱导毒性后处理细胞系时，细胞活力增加，凋亡和ROS/RNS产生显著减少，KIM-1和NGAL的表达显著降低。
结论 本研究表明，在体外环境中，TG对药物性肾毒性的恢复具有积极作用。
