顺铂引起的肾毒性限制了其针对实体瘤的临床应用。本研究利用顺铂诱导的人肾近端小管 (HK-2) 细胞和秀丽隐杆线虫，阐明了 Renogrit（一种植物源处方药）的药理作用。 Renogrit 中植物化学物质的定量是在 HPTLC 和 UHPLC 平台上进行的。在暴露于临床相关浓度的顺铂后，在体外对 HK-2 细胞中的 Renogrit 进行评估。据观察，Renogrit 对顺铂引起的损伤的肾脏保护特性源于其调节肾损伤标志物（KIM-1、NAG 水平；NGAL mRNA 表达）、氧化还原失衡（ROS 生成；GST 水平）和线粒体功能障碍（线粒体功能）的能力。膜电位；SKN-1、HSP-60 表达）。 Renogrit 还被发现可以调节细胞凋亡（EGL-1 mRNA 表达；p-ERK、p-JNK、p-p38、c-PARP1 的蛋白水平）、坏死性凋亡（细胞内钙积累；RIPK1、RIPK3、MLKL mRNA 表达）、线粒体自噬（溶酶体群体；PINK1、PDR1 的 mRNA 表达；p-PINK1、LC3B 的蛋白水平）和炎症（IL-1β 活性；LXR-α 的蛋白水平）。更重要的是，根据对 MCF-7、A549、SiHa 和 T24 人类癌细胞的细胞毒性分析观察到，Renogrit 治疗不会妨碍顺铂的正常抗增殖作用。总而言之，Renogrit 可能成为减轻顺铂引起的肾毒性而不损害顺铂抗肿瘤特性的潜在临床候选药物。© 2024。作者。

Cisplatin-induced nephrotoxicity restricts its clinical use against solid tumors. The present study elucidated the pharmacological effects of Renogrit, a plant-derived prescription medicine, using cisplatin-induced human renal proximal tubular (HK-2) cells and Caenorhabditis elegans. Quantification of phytochemicals in Renogrit was performed on HPTLC and UHPLC platforms. Renogrit was assessed in vitro in HK-2 cells post-exposure to clinically relevant concentration of cisplatin. It was observed that renoprotective properties of Renogrit against cisplatin-induced injury stem from its ability to regulate renal injury markers (KIM-1, NAG levels; NGAL mRNA expression), redox imbalance (ROS generation; GST levels), and mitochondrial dysfunction (mitochondrial membrane potential; SKN-1, HSP-60 expression). Renogrit was also found to modulate apoptosis (EGL-1 mRNA expression; protein levels of p-ERK, p-JNK, p-p38, c-PARP1), necroptosis (intracellular calcium accumulation; RIPK1, RIPK3, MLKL mRNA expression), mitophagy (lysosome population; mRNA expression of PINK1, PDR1; protein levels of p-PINK1, LC3B), and inflammation (IL-1β activity; protein levels of LXR-α). More importantly, Renogrit treatment did not hamper normal anti-proliferative effects of cisplatin as observed from cytotoxicity analysis on MCF-7, A549, SiHa, and T24 human cancer cells. Taken together, Renogrit could be a potential clinical candidate to mitigate cisplatin-induced nephrotoxicity without compromising the anti-neoplastic properties of cisplatin.© 2024. The Author(s).