Selenium Supplementation Protects Against Arsenic-Trioxide-Induced Cardiotoxicity Via Reducing Oxidative Stress and Inflammation Through Increasing NAD+ Pool

Abstract

Arsenic is an environmental contaminant, and accumulating evidence has indicated that exposure to arsenic can cause various diseases, especially cardiotoxicity. Selenium (Se) exerts a vital role in the regulation of multiple physiological activities. Recently, several studies highlighted that Se treatment can effectively antagonize the toxic effects induced by arsenic. However, the exact underlying effect and mechanism of Se on Arsenic-induced cardiotoxicity has not been explored. In the current study, the arsenic trioxide (ATO)-triggered heart damage mice model was used to explore whether Se exerts protective roles in ATO-related cardiotoxicity and its potential mechanism. Our data showed that Se treatment significantly alleviated ATO-mediated cardiotoxicity evidenced by increased weight, decreased myocardial damage markers, and improved heart functions in mice. Furthermore, we demonstrated that Se remarkably inhibited ATO-mediated oxidative stress and inflammatory responses in heart tissues. Mechanistically, we showed that Se upregulated the levels of NAD⁺ in cardiomyocytes of the mice challenged by ATO, and this effect involved in the activation of the NAD⁺ biosynthesis through the salvage pathway. Collectively, our findings demonstrated that Se protected against ATO-mediated cardiotoxicity by antioxidant and anti-inflammatory effects via increasing the NAD⁺ pool in mice.

Keywords: Arsenic trioxide; Cardiotoxicity, NAD+; Selenium.