Bismuth Reduces Cisplatin-Induced Nephrotoxicity Via Enhancing Glutathione Conjugation and Vesicular Transport.

ABSTRACT: Bismuth drugs have long been used against gastrointestinal diseases, especially the gastric infection of Helicobacter pylori. Cisplatin is a widely used anticancer drug that tends to accumulate at renal proximal tubules and causes severe nephrotoxicity. It was found that bismuth pretreatment reduces cisplatin-induced nephrotoxicity, but the mechanism of action remains unclear. To understand bismuth's effect on renal tubules, we profiled the proteomic changes in human proximal tubular cells (HK-2) upon bismuth treatment. We found that bismuth induced massive glutathione biosynthesis, glutathione S-transferase activity, and vesicular transportation, which compartmentalizes bismuth to the vesicles and forms bismuth-sulfur nanoparticles. The timing of glutathione induction concurs that

SUBMITTER: Jiang H 

PROVIDER: S-EPMC9243339 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature