The action of low doses of persistent organic pollutants (POPs) on mitochondrial function in zebrafish eyes and comparison with hyperglycemia to identify a link between POPs and diabetes

Toxicol Mech Methods. 2020 May;30(4):275-283. doi: 10.1080/15376516.2020.1717704. Epub 2020 Jan 28.

Abstract

Type 2 diabetes (T2D) is characterized by defects in insulin action to target tissues, resulting in hyperglycemia, insulin resistance, and mitochondrial dysfunction. The eye is one of the organs susceptible to T2D, but knowledge regarding mitochondrial dysfunction in the eyes after hyperglycemia and T2D is based mainly on epidemiological evidence, with little experimental data. Persistent organic pollutants (POPs) are known as endocrine-disrupting chemicals and are associated with uncontrolled glucose and lipid metabolism, leading to the onset of diabetes. To determine the relationship between POPs and T2D, two model systems were developed: glucose-immersed zebrafish to induce hyperglycemia, and zebrafish exposed to low-dose POPs in a water circulating system for three months. To examine the role of mitochondrial function, the activity of mitochondrial complexes I, II, III, and IV from the eyes of the two zebrafish models was measured spectrophotometrically. Enhanced enzymatic activities of mitochondrial complexes III and IV were observed in the eyes of both hyperglycemia and low-dose POPs exposed models, especially in male zebrafish. These results demonstrate that POPs alleviate mitochondrial oxidative phosphorylation (OXPHOS) in a sex-dependent manner through a compensatory mechanism, which is also observed in acute hyperglycemia.

Keywords: Eye; Zebrafish; hyperglycemia; mitochondrial oxidative phosphorylation; persistent organic pollutant.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 2 / metabolism*
  • Electron Transport Complex III / metabolism
  • Electron Transport Complex IV / metabolism
  • Hydrocarbons, Chlorinated / toxicity*
  • Hyperglycemia / metabolism*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Phosphorylation
  • Persistent Organic Pollutants / toxicity*
  • Retina / drug effects*
  • Retina / metabolism
  • Zebrafish / metabolism*

Substances

  • Blood Glucose
  • Hydrocarbons, Chlorinated
  • Electron Transport Complex IV
  • Electron Transport Complex III