Developmental toxicity of flufenacet including vascular, liver, and pancreas defects is mediated by apoptosis and alters the Mapk and PI3K/Akt signal transduction in zebrafish

Abstract

Release of agrochemicals from agricultural fields could unintentionally harm organisms that not targeted by pesticides. Flufenacet is one of the oxyacetamide herbicide applied in cultivation fields of crops and this has a possibility of unintentional exposure to diverse ecosystems including streams and surface water. Despite these environmental risks, limited information regarding toxicity of flufenacet on vertebrates is available. This study is aimed to assess environmental hazards and underlying toxic mechanisms of flufenacet by using a zebrafish model. Mortality measurements and morphological observations after the treatment of flufenacet suggested developmental toxicity of flufenacet in zebrafish. In addition, its toxicity on specific organs was evaluated using transgenic fluorescent zebrafish embryo. Adverse effects of flufenacet on vascular and hepatopancreatic development were demonstrated using Tg(flk1:EGFP) and Tg(fabp10a:DsRed; ela3l:EGFP) respectively. To address intracellular actions of flufenacet in zebrafish, cellular responses including apoptosis, cell cycle modulation, and Mapk and Akt signaling pathway were verified in transcriptional and protein levels. These results demonstrated developmental toxicity of flufenacet using the zebrafish model, providing essential information for assessing its potential hazards on vertebrates that are not directly targeted by the pesticide and for elucidating molecular mechanisms.