Bottom-line mechanism of organochlorine pesticides on mitochondria dysfunction linked with type 2 diabetes

J Hazard Mater. 2020 Jul 5;393:122400. doi: 10.1016/j.jhazmat.2020.122400. Epub 2020 Feb 25.

Abstract

Environmental pollution by anthropogenic chemicals has become a considerable problem. Organochlorine pesticides (OCPs), a subclass of persistent organic pollutants, are used as insecticides and industrial chemicals. They are lipophilic and minimally degradable, and they easily accumulate in the environment and human body. Epidemiological studies have demonstrated that exposure to OCPs strongly correlates with the development of type 2 diabetes, which involves mitochondrial dysfunction. To clarify their effects, OCP mixtures (β-hexachlorocyclohexane, heptachlor, hexachlorobenzene, 4,4'-DDT, and chlordane) were used to treat mitochondria from zebrafish livers. Results showed that as OCP concentrations increased, Ca2+ intake into the mitochondria rose, which increased the activity of mitochondrial complexes I, II, IV, and citrate synthase. Complex III yielded the opposite result because the OCP mixture mimicked decylubiquinol, a natural substrate of complex III. Our results reflect the actual state of toxins, non-monotonic, in the environment, which is important for determining the consequences of OCPs on mitochondrial dysfunction.

Keywords: Competitive inhibitor; Diabetes; Ion regulator; Mitochondrial dysfunction; Organochlorine pesticides (OCPs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2
  • Electron Transport Chain Complex Proteins / metabolism
  • Female
  • Hydrocarbons, Chlorinated / toxicity*
  • Male
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Pesticides / toxicity*
  • Zebrafish
  • Zebrafish Proteins / metabolism

Substances

  • Electron Transport Chain Complex Proteins
  • Hydrocarbons, Chlorinated
  • Pesticides
  • Zebrafish Proteins