Cadmium potentiates toxicity of cypermethrin in zebrafish

Environ Toxicol Chem. 2016 Feb;35(2):435-45. doi: 10.1002/etc.3200. Epub 2016 Jan 8.

Abstract

Co-occurrence of pesticides such as synthetic pyrethroids and metals in aquatic ecosystems raises concerns over their combined ecological effects. Cypermethrin, 1 of the top 5 synthetic pyrethroids in use, has been extensively detected in surface water. Cadmium (Cd) has been recognized as 1 of the most toxic metals and is a common contaminant in the aquatic system. However, little information is available regarding their joint toxicity. In the present study, combined toxicity of cypermethrin and Cd and the underlying mechanisms were investigated. Zebrafish embryos and adults were exposed to the individual contaminant or binary mixtures. Co-exposure to cypermethrin and Cd produced synergistic effects on the occurrence of crooked body, pericardial edema, and noninflation of swim bladder. The addition of Cd significantly potentiated cypermethrin-induced spasms and caused more oxidative stress in zebrafish larvae. Cypermethrin-mediated induction of transcription levels and catalytic activities of cytochrome P450 (CYP) enzyme were significantly down-regulated by Cd in both zebrafish larvae and adults. Chemical analytical data showed that in vitro elimination of cypermethrin by CYP1A1 was inhibited by Cd. The addition of Cd caused an elevation of in vivo cypermethrin residue levels in the mixture-exposed adult zebrafish. These results suggest that the enhanced toxicity of cypermethrin in the presence of Cd results from the inhibitory effects of Cd on CYP-mediated biotransformation of this pesticide. The authors' findings provide a deeper understanding of the mechanistic basis accounting for the joint toxicity of cypermethrin and Cd.

Keywords: Cadmium; Cypermethrin; Cytochrome P450; Pyrethroid; Toxicity; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced / pathology
  • Air Sacs / abnormalities
  • Air Sacs / pathology
  • Animals
  • Antioxidants / metabolism
  • Cadmium / toxicity*
  • Cytochrome P-450 CYP1A1 / antagonists & inhibitors
  • Cytochrome P-450 CYP1A1 / metabolism
  • Drug Synergism
  • Edema / chemically induced
  • Edema / pathology
  • Gene Expression / drug effects
  • Insecticides / pharmacokinetics
  • Insecticides / toxicity*
  • Larva
  • Lethal Dose 50
  • Pericardium / pathology
  • Pesticide Residues / toxicity
  • Pyrethrins / pharmacokinetics
  • Pyrethrins / toxicity*
  • Tail / abnormalities
  • Water Pollutants, Chemical / toxicity*
  • Zebrafish*

Substances

  • Antioxidants
  • Insecticides
  • Pesticide Residues
  • Pyrethrins
  • Water Pollutants, Chemical
  • Cadmium
  • cypermethrin
  • Cytochrome P-450 CYP1A1