Polylactic acid nanoplastics induce kidney injury by activating the TRPM2-mediated mitophagy pathway.

Abstract

Polylactic acid nanoparticles (PLA NPs) are widely used biodegradable plastics, but their potential health risks remain unclear. This study explores whether PLA NPs induce renal cell apoptosis through a mitochondrial pathway involving transient receptor potential melastatin 2 (TRPM2) and mitophagy. Adult male C57BL/6 mice were orally exposed to 0.1, 1, and 10 mg/kg/day PLA NPs for 28 consecutive days. PLA NPs caused dose-dependent kidney injury, with the high-dose group (group H, 10 mg/kg/day) showing the most severe renal apoptosis and functional impairment. In group H, renal calcium ion (Ca2+) levels, mitophagy, and TRPM2 expression were significantly elevated. To investigate the mechanism, TRPM2-KO mice (group KH) and mitophagy inhibitor Mdivi-1-treated mice (group Md) were orally administered 10 mg/kg/day PLA NPs daily. Compared with group H, both group KH and group Md showed reduced renal injury, as evidenced by decreased apoptosis and restored mitochondrial function. These results indicate that PLA NPs induce oxidative stress, activate the TRPM2 channel, cause calcium overload and excessive mitophagy, and ultimately trigger renal cell apoptosis. This study provides a theoretical basis for targeted treatment of kidney diseases caused by PLA NPs.