Exposure to Mancozeb results in increased MAPK phosphorylation and locomotor deficits in zebrafish larvae

Comp Biochem Physiol C Toxicol Pharmacol. 2023 Aug:270:109659. doi: 10.1016/j.cbpc.2023.109659. Epub 2023 May 17.

Abstract

Mancozeb is a widely used fungicide whose toxicity has been reported in non-target organisms, being considered to have high or very high acute toxicity to aquatic organisms. However, the toxicity of this compound is not well characterized in the developmental stages of fish. In this study, Danio rerio with 4-, 5-, and 6-days post fertilization (dpf) was exposed to MZ at non-lethal concentrations for 24, 48, or 72 h and subsequently, behavioral alterations, oxidative stress parameters and ERK, p38MAPK, and Akt phosphorylation were analyzed. MZ exposure during the larval period decreased motor performance evaluated by traveled distance, immobile time, and time spent in the peripheral area. In parallel, MZ induced ROS levels and increased the number of cells in apoptosis, causing severe DNA damage, inducing Acetylcholinesterase and Superoxide dismutase activities, and inhibiting Glutathione peroxidase and thioredoxin reductase. Additionally, phosphorylation levels of the proteins p38MAPK, ERK2, and Akt were stimulated. These findings are relevant considering the ecological implications of MZ exposure to fishes in different developmental stages and the role of the MAPK pathway in events like development and cell death.

Keywords: Acetylcholinesterase; Apoptosis; DNA damage; Danio rerio; Dithiocarbamates.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Embryo, Nonmammalian / metabolism
  • Larva / metabolism
  • Oxidative Stress
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Water Pollutants, Chemical* / toxicity
  • Zebrafish* / metabolism

Substances

  • mancozeb
  • Acetylcholinesterase
  • Proto-Oncogene Proteins c-akt
  • Water Pollutants, Chemical