Resveratrol attenuates trimethyltin chloride-induced cardiac defects via the ROS/Wnt/β-catenin pathway

Oct 13, 2025Comparative biochemistry and physiology. Toxicology & pharmacology : CBP

Resveratrol reduces heart defects caused by trimethyltin chloride through the oxidative stress and Wnt/beta-catenin signaling pathway

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

TMT exposure increased pericardial area by 44.9% and decreased heart rate by 16.8% in zebrafish embryos.

TMT exposure is associated with dose-dependent cardiac malformations in zebrafish embryos.
Excessive reactive oxygen species (ROS) generation increased by 48.5%, while mitochondrial ROS generation rose by 82.8% after TMT exposure.
Co-treatment with resveratrol or the ROS inhibitor N-acetylcysteine reduced TMT-induced cardiac defects and ROS overproduction.
TMT inhibited the Wnt/β-catenin signaling pathway by 61.7%, contributing to cardiac malformations.
Resveratrol or N-acetylcysteine mitigated DNA damage, mitochondrial injury, and apoptosis in the heart.

AI simplified

Trimethyltin chloride (TMT), a toxic byproduct of organotin manufacturing, is an emerging environmental contaminant linked to developmental cardiotoxicity. However, its pathogenic mechanism remains undefined. Here, using zebrafish embryos, we show that TMT exposure induced dose-dependent cardiac malformations, increasing pericardial area by 44.9 % and decreasing heart rate by 16.8 % at 5 μM (both P < 0.001), accompanied by excessive ROS (+48.5 %, P < 0.001) and mitochondrial ROS (+82.8 %, P < 0.001) generation. Co-treatment with resveratrol (RSV) or the ROS inhibitor N-acetylcysteine (NAC) reduced TMT-induced cardiac defects and suppressed ROS and mitochondrial ROS overproduction (all P < 0.05). RSV or NAC also mitigated DNA damage, mitochondrial injury, and apoptosis in the heart. Mechanistically, TMT inhibited the Wnt/β-catenin signaling pathway (-61.7 % β-catenin, P < 0.001), an effect attenuated by RSV or NAC. Inhibition of apoptosis with Ac-DEVD-CHO or activation of Wnt/β-catenin signaling with CHIR likewise alleviated TMT-induced cardiac malformations. These results indicate that TMT disrupts heart development through ROS-mediated suppression of Wnt/β-catenin signaling, leading to mitochondrial damage, DNA damage, and apoptosis. Furthermore, RSV, a dietary antioxidant, provides significant protection against TMT-induced cardiac developmental toxicity. This study identifies potential molecular targets for preventing and treating embryonic heart injury caused by environmental toxicants.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Resveratrol attenuates trimethyltin chloride-induced cardiac defects via the ROS/Wnt/β-catenin pathway

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief