Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Toxicol In Vitro. 2021 Sep;75:105179. doi: 10.1016/j.tiv.2021.105179. Epub 2021 Apr 24.
Renal toxicants such as cisplatin and cadmium cause segment-specific damages in kidney proximal tubules. Recently, we established an in vitro experimental system for evaluating segment-specific toxicity and transport of chemicals using immortalized S1, S2, and S3 cells derived from the S1, S2, and S3 regions of mouse kidney proximal tubules. In the present study, we examined the toxicity and accumulation of cisplatin, carboplatin, oxaliplatin, and cadmium in S1, S2, and S3 cells. We found that not only cisplatin but also carboplatin and oxaliplatin exhibited higher lethal toxicity in S3 cells than in S1 and S2 cells. At sublethal doses, cisplatin showed delayed induction of Kim-1 and clusterin on days 3 and 6, which may reflect the latent renal toxicity of cisplatin in vivo. The high sensitivities of S3 cells to the platinum-based agents were not due to the high accumulation of Pt in S3 cells. Exposure to cadmium resulted in similar toxicity among these cells, suggesting that S3 cells were not sensitive to any renal toxicants. Thus, the utilization of S1, S2, and S3 cells may provide a useful tool for the in vitro evaluation of the proximal tubule segment-specific toxicity of chemicals.
肾毒物如顺铂和镉会导致肾脏近端小管的特定节段损伤。最近，我们建立了一种体外实验系统，用于评估使用源自小鼠肾脏近端小管 S1、S2 和 S3 区的永生化 S1、S2 和 S3 细胞评估化学物质的特定节段毒性和转运。在本研究中，我们研究了顺铂、卡铂、奥沙利铂和镉对 S1、S2 和 S3 细胞的毒性和积累。我们发现，不仅顺铂，而且卡铂和奥沙利铂在 S3 细胞中的致死毒性均高于 S1 和 S2 细胞。在亚致死剂量下，顺铂在第 3 天和第 6 天延迟诱导 Kim-1 和簇蛋白的表达，这可能反映了顺铂在体内的潜在肾毒性。S3 细胞对铂类药物的高敏感性并不是由于 S3 细胞中 Pt 的高积累所致。镉暴露导致这些细胞之间具有相似的毒性，表明 S3 细胞对任何肾毒物均不敏感。因此，S1、S2 和 S3 细胞的利用可能为体外评估化学物质的近端小管特定节段毒性提供有用的工具。
