Particulate matter (PM10) induces cardiovascular developmental toxicity in zebrafish embryos and larvae via the ERS, Nrf2 and Wnt pathways

Chemosphere. 2020 Jul;250:126288. doi: 10.1016/j.chemosphere.2020.126288. Epub 2020 Feb 22.

Abstract

Particulate matter (PM10) is one of the most important indicators of the pollution that characterizes air quality. Epidemiological studies have shown that PM10 can cause cardiovascular-related diseases in the population. And, we studied the developmental toxicity of PM10 and the underlying mechanism of its effects on the cardiovascular system of zebrafish embryo/larva. Changes in cardiac morphology, sinus venosus and bulbus arteriosus (SV-BA) distance, heart rate, vascular subintestinalis, blood flow, returned blood volume, and reactive oxygen species (ROS) level were measured, and changes in the expression levels of certain genes were assessed via RT-PCR. The results showed that PM10 caused a significant increase in pericardial sac area and SV-BA distance, a decrease in heart rate, inhibition of vascular subintestinalis growth, blood flow obstruction, reduced venous return, and other cardiovascular toxicities. PM10 induced an increase in the ROS level and significant increases in the expression levels of ERS signalling pathway factors and Nrf2 signalling pathway factors. The expression levels of the Wnt pathway-related genes also showed significant changes. Furthermore, ROS inhibitor N-Acetyl-l-cysteine (NAC) could ameliorate the cardiovascular toxicity of PM10 in zebrafish larvae. It is speculated that PM10 may result in cardiovascular toxicity by inducing higher ROS levels in the body, which could then induce ERS and lead to defects in the expression of genes related to the Wnt signalling pathway. The Nrf2 signalling pathway was activated as a stress compensatory mechanism during the early stage of PM10-induced cardiovascular injury. However, it was insufficient to counteract the PM10-induced cardiovascular toxicity.

Keywords: Cardiovascular toxicity; ERS; Nrf2; PM10; Wnt.

MeSH terms

  • Animals
  • Cardiovascular System / drug effects*
  • Embryo, Nonmammalian / drug effects*
  • Larva / drug effects*
  • Larva / metabolism
  • NF-E2-Related Factor 2 / drug effects
  • NF-E2-Related Factor 2 / metabolism
  • Organogenesis
  • Particulate Matter / toxicity*
  • Reactive Oxygen Species / metabolism
  • Wnt Signaling Pathway / drug effects
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics

Substances

  • NF-E2-Related Factor 2
  • Particulate Matter
  • Reactive Oxygen Species
  • Zebrafish Proteins