In vivo cardiovascular toxicity induced by acetochlor in zebrafish larvae

Chemosphere. 2017 Aug:181:600-608. doi: 10.1016/j.chemosphere.2017.04.090. Epub 2017 Apr 21.

Abstract

The risk of acetochlor to human health is still unclear, prompting concern over its risk, especially to pesticide suicides population, occupational population (farmers, retailers and pharmaceutical workers), and special population (young children and infants, pregnant women, older people, and those with compromised immune systems). This study was to explore the toxic effect and the possible mechanism of toxic action of acetochlor using zebrafish larvae whose toxicity profiles have been confirmed to be strikingly similar with mammalian. The result indicated that the toxic target organ of acetochlor was cardiovascular system. Thus, cardiovascular toxicity evaluation was investigated systematically. The main phenotypes of cardiovascular toxicity induced by acetochlor were bradycardia, pericardial edema, circulation defect, and thrombosis; Malformed heart was confirmed by histopathological examination. Thrombosis which maybe triggered by bradycardia was further studied using o-dianisidine for erythrocyte staining; Substantial thrombus in the caudal vein and significantly reduced heart red blood cells (RBCs) intensity which can reflect the thrombosis degree were observed in zebrafish in a concentration-dependent manner. Additionally, the mRNA expression level of Nkx2.5 and Gata4 related to induction of cardiac program were down-regulated significantly by quantitative real-time polymerase chain reaction (qRT-PCR), which could cause defects in the cardiovascular system. For the first time, our results demonstrated that acetochlor induced cardiovascular toxicity, and down-regulation of Nkx2.5 and Gata4 might be its possible molecular basis. Our data generated here might provide novel insights into cardiovascular disease risk following acetochlor exposure to human, especially to pesticide suicides population, occupational population and special population.

Keywords: Acetochlor; Cardiovascular toxicity; Health risk; Zebrafish.

MeSH terms

  • Animals
  • Cardiovascular System / drug effects*
  • Down-Regulation
  • GATA Transcription Factors / genetics
  • Herbicides / toxicity
  • Homeobox Protein Nkx-2.5 / genetics
  • Humans
  • Larva / drug effects*
  • RNA, Messenger / metabolism
  • Toluidines / toxicity*
  • Zebrafish Proteins / genetics
  • Zebrafish*

Substances

  • GATA Transcription Factors
  • Gata4 protein, zebrafish
  • Herbicides
  • Homeobox Protein Nkx-2.5
  • Nkx2.5 protein, zebrafish
  • RNA, Messenger
  • Toluidines
  • Zebrafish Proteins
  • acetochlor