Triadimenol Promotes the Production of Reactive Oxidative Species and Apoptosis with Cardiotoxicity and Developmental Abnormalities in Zebrafish

Abstract

It is important to prevent fungal diseases to maintain agricultural production since approximately 70% of plant diseases are caused by fungi. Various types of fungicides are used to prevent such diseases, and the rate of the usage of triazole fungicides is more than that of other fungicides. Therefore, triazole fungicides have been detected in various environments, and numerous toxic effects in non-target organisms have also been reported. However, the toxicity of triadimenol, particularly developmental toxicity, remains unclear. Therefore, we used the zebrafish animal model, a representative toxicological model, to investigate mechanisms associated with the developmental toxicities induced by triadimenol. Triadimenol induced morphological alterations in the eyes and body length along with yolk sac and heart edema. It also stimulated the production of reactive oxygen species and expression of inflammation-related genes and caused apoptosis in the anterior regions of zebrafish, especially in the heart. The phosphorylation levels of akt, erk, jnk, and p38 proteins involved in the PI3K and MAPK pathways, which are important for the development process, were also reduced by triadimenol. These changes led to malformation of the heart and vascular structures, as observed in the flk1:eGFP transgenic zebrafish models and a reduction in the heart rate. In addition, the expression of genes associated with cardiac and vascular development was also reduced. Therefore, we elucidated the mechanisms associated with triadimenol toxicity that leads to various abnormalities and developmental toxicity in zebrafish.

Keywords: zebrafish model, triadimenol, reactive oxygen species production, apoptosis, Cardiotoxicity