Mitigating PM2.5 Induced Myocardial Metal Deposition Through Sodium Thiosulfate Resulted in Reduction of Cardiotoxicity and Physiological Recovery From Ischemia-Reperfusion via Mitochondrial Preservation.

Abstract

The cardiovascular risks linked to PM_2.5 include calcification in both vasculature and myocardial tissues, leading to structural changes and functional decline. Through the selection of a clinically proven endogenous agent, sodium thiosulfate (STS), capable of addressing PM_2.5 related cardiac abnormalities, we not only address the absence of effective solutions to mitigate PM_2.5 toxicity, but also provide evidence for the repurposing potential of STS in ameliorating PM_2.5 induced cardiac damage. Female Wistar rats were exposed to PM_2.5 (250 μg/m³) for 3 h daily for 21 days. STS was administered thrice weekly for 3 weeks during exposure after which the hearts were excised and mounted on a Langendorff apparatus for induction of ischemia-reperfusion injury (IR). STS administration improved cardiac function in PM_2.5 exposed rat hearts, accompanied by increased expression of the master regulator gene PGC1-α and increased mitochondrial mass. Moreover, STS restored bioenergetic function and balanced mitochondrial fission-fusion dynamics. The beneficial effects of STS were further evidenced by its ability to scavenge metals, thereby reducing heavy metal deposition in mitochondria and alleviating oxidative stress and inflammation. Furthermore, STS facilitated the clearance of damaged mitochondria through mitophagy. Additionally, STS activated the PI3K/AKT/GSK3ß signaling pathway, providing cardio protection against IR injury in PM_2.5-exposed hearts by preserving mitochondrial function. These results underscore the potential therapeutic benefits of STS in mitigating the adverse cardiac effects induced by PM_2.5 exposure. The translation of these findings to clinical practice holds promise for the development of targeted interventions aimed at reducing the cardiovascular toxicity associated with PM_2.5 exposure.