Chlorpyrifos cardiotoxic responses may be mediated by phagocytic activation in larval zebrafish

Abstract

Chlorpyrifos, an organophosphate insecticide, is used throughout the world, with frequent detections being reported in both surface and ground water. The neurotoxic effects of chlorpyrifos have been thoroughly investigated. However, chlorpyrifos-induced cardiotoxicity has also been observed in fish and remains poorly understood. In the present study, zebrafish (Danio rerio) larvae (7 days post hatch) were exposed to environmentally relevant concentrations of chlorpyrifos ranging from 0.01 to 100 μg/L. A decline in heart rate was observed in animals treated with 10 and 100 μg/L (8.57 % and 15.13 %, respectively). Using in silico bioinformatics of the transcriptome following exposure, the top enriched pathways were predicted to be involved in cardiac and immune dysfunction. Consistent with impacts predicted by transcriptional changes, statistical, but non-concentration-dependent increases were also observed in macrophage number, IL-6 and TNF-α levels, and phagocytic function. Since chlorpyrifos-induced immune effects were associated with Rho GTPase pathways identified in bioinformatic predictions, treatments with the positive control, N-Acetylneuraminic acid, or a Rac family small GTPase antagonist (EHT 1864), respectively enhanced and reversed cardiotoxicity. This indicated a potential role for Rho GTPase signaling in chlorpyrifos-induced cardiotoxic and immune response effects. The data presented underscores the interaction between cardiotoxic and immune functional responses following exposure to environmentally relevant levels of chlorpyrifos and the potential role of immune system alterations as a key event in adverse outcome pathways for cardiotoxicity.