The present study assessed the therapeutic potential of omeprazole (OME), the most commonly prescribed proton pump inhibitor (PPI) used to treat gastroesophageal hyperacidity, against cisplatin (CP)-induced toxicity in human renal tubular HK-2 cells and rat kidneys. Herein, we observed that exposure of HK-2 cells to OME reversed the injury caused by CP, including enhancing cell viability and alleviating intracellular reactive oxygen species (ROS) generation and membrane damage. Concomitantly, acute exposure of male SD rats to CP induced histopathological changes, which were prevented by co-administration with OME. Inflammation and oxidative stress were inhibited by OME during CP-induced renal injury by increasing the activity of superoxide dismutase, and reducing the levels of malondialdehyde, both in vivo and in vitro. The expression levels of major inflammatory response markers were significantly decreased in HK-2 cells and rat kidneys in response to OME. OME reduced CP cellular uptake through organic cation transporters 2 (OCT2) and the prompt efflux of CP by P-glycoprotein (P-gp), thereby reducing the accumulation of CP in kidney tissue and increasing its serum levels. These data demonstrate that CP-induced kidney damage is positively correlated with its cellular accumulation. Concurrently, OME showed renoprotective effect against CP-induced toxicity in HK-2 cells and rat kidneys, by suppressing oxidative stress and mediating NF-κB-dependent inflammation, apoptosis, and transporter function. As OME is commonly used in combination with CP during chemotherapy treatment, this study highlights the clinical significance of OME in alleviating CP-induced nephrotoxicity.

本研究评估了用于治疗胃食管酸过多的最常用处方质子泵抑制剂（PPI）奥美拉唑（OME）对顺铂（CP）诱导的人肾小管HK-2细胞和大鼠肾脏毒性的治疗潜力。在本文中，我们观察到HK-2细胞暴露于OME可以逆转CP引起的损伤，包括增强细胞活力并减轻细胞内活性氧（ROS）的产生和膜损伤。同时，雄性SD大鼠急性暴露于CP引起组织病理学改变，与OME并用可预防这种改变。通过在体内和体外增加超氧化物歧化酶的活性并降低丙二醛的水平，OME在CP诱导的肾损伤期间抑制了炎症和氧化应激。响应OME，HK-2细胞和大鼠肾脏中主要炎症反应标志物的表达水平显着降低。OME减少了CP通过有机阳离子转运蛋白2（OCT2）的吸收，并通过P-糖蛋白（P-gp）迅速释放CP，从而减少了CP在肾脏组织中的积累并增加了其血清水平。这些数据表明，CP诱导的肾损害与其细胞蓄积正相关。同时，OME通过抑制氧化应激并介导NF-κB依赖性炎症，凋亡和转运蛋白功能，对HK-2细胞和大鼠肾脏中CP诱导的毒性表现出了肾脏保护作用。由于在化疗期间OME通常与CP结合使用，