Dimethyl sulfate induces zebrafish embryo cardiotoxicity and behavioral disturbances by upregulating oxidative stress levels

Abstract

Dimethyl sulfate (DMS) is a versatile chemical compound used in various industries, including pharmaceuticals, pesticides, dyes, and fragrances. Due to the widely application of Dimethyl sulfate (DMS), it is necessary to study its potential toxicity. According to ecological data analysis, DMS has been identified as a potential environmental hazard, particularly in water bodies. However, its toxicity to aquatic organisms remains largely unexplored. In this study, using zebrafish embryos as a model system, we evaluated the toxicity of DMS for the first time and uncovered significant adverse effects on early embryonic development, characterized by extensive cardiac damage and neurotoxicity. DMS inhibited the activity of antioxidant enzymes, resulting in excessive production of reactive oxygen species (ROS) and subsequent apoptosis of myocardial cells, along with pericardial edema, bradycardia, and elongated SV-BA distance. Additionally, DMS directly induced oxidative stress and altered the activity of acetylcholinesterase (ACHE) and adenosine triphosphatase (ATPase), thereby disrupting the expression of genes involved in neural development and neurotransmission. These findings may contribute to the DMS-induced behavioral abnormalities, such as reduced and unbalanced locomotion in larvae and altered swimming behavior. Importantly, astaxanthin, an antioxidant carotenoid, was able to rescue the embryonic cardiac and neurotoxic effects triggered by DMS exposure, suggesting that DMS primarily induces zebrafish cardiac and neural developmental toxicity through upregulation of oxidative stress. Overall, our study demonstrates the potential of DMS to induce cardiac and neurotoxicity in zebrafish embryos, suggesting toxicity risks to other aquatic organisms and even humans. These findings provide a basis for a comprehensive assessment of DMS toxicity and serve as an early warning for its environmental presence and product residues.