Resveratrol protects against PM2.5-induced heart defects in zebrafish embryos as an antioxidant rather than as an AHR antagonist.

Resveratrol (RSV), a natural polyphenolic compound commonly found in food, has antioxidant and aryl hydrocarbon receptor (AHR) antagonist effects. We have recently demonstrated that AHR mediated reactive oxygen species (ROS) generation contributes to the cardiac developmental toxicity of ambient fine particle matter (PM2.5). Thus, we hypothesized that RSV protects against the cardiac developmental toxicity of PM2.5 by inhibiting ROS generation and AHR activity. To test this concept, we exposed zebrafish embryos to extractable organic matter (EOM) from PM2.5 in the presence or absence of RSV. We found that RSV significantly counteracted EOM-induced cardiac malformations in zebrafish embryos. The EOM-induced ROS production, DNA damage and apoptosis in the heart of zebrafish embryos were also counteracted by RSV supplementation. Furthermore, RSV attenuated EOM-induced changes in the expression of genes involved in cardiac development (nkx2.5, sox9b, axin2), oxidative stress (nrf2a, nrf2b, gstp1, gstp2, sod1, sod2, cat) and apoptosis (p53, bax). However, RSV did not suppress EOM-induced AHR activity. In conclusion, our data indicates that RSV protects against the PM2.5-induced heart malformations by inhibiting oxidative stress rather than through AHR antagonism.