Effects of atrazine on hepatic metabolism and endocrine homeostasis in rainbow trout (Oncorhynchus mykiss)

Toxicol Appl Pharmacol. 2009 Jan 1;234(1):98-106. doi: 10.1016/j.taap.2008.09.023. Epub 2008 Oct 10.

Abstract

The herbicide atrazine (ATZ) is one of the most widely used pesticides in the world and is now under scrutiny for its alleged capacity to disrupt the endocrine system. Exhibiting negligible interaction with the estrogen receptor (ER), ATZ's mode of action remains to be elucidated. ATZ may act as an inducer of the enzyme aromatase, which converts androgens to estrogens, although other mechanisms should also be taken into consideration such as impairment of hepatic metabolism. Therefore we administered juvenile rainbow trout (Oncorhynchus mykiss) a dose of either 2 or 200 microg ATZ/kg, or of carrier control phosphate buffered saline (PBS) and we measured plasma concentrations of testosterone (T), 17beta-estradiol (E2) and vitellogenin (Vtg) 6 days after exposure. Simultaneously we analyzed hepatic gene expression of cytochrome P450 (CYP) 1A and pi-class glutathione S-transferase (GST-P), and catalase (CAT) activity. Although sex steroid levels showed no significant alterations, we found a dose-dependent increase in Vtg and a concomitant decrease in CYP1A. There was no effect of ATZ on GST-P mRNA levels but GST-P was positively correlated with CYP1A. Also, CYP1A was negatively correlated with liver CAT and E2, and varied with T concentrations in a hormetic manner. The results showed that ATZ can alter hepatic metabolism, induce estrogenic effects and oxidative stress in vivo, and that these effects are linked.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / drug effects
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Atrazine / administration & dosage
  • Atrazine / toxicity*
  • Catalase / drug effects
  • Catalase / metabolism
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / administration & dosage
  • Endocrine Disruptors / toxicity*
  • Estradiol / blood
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Glutathione S-Transferase pi / drug effects
  • Glutathione S-Transferase pi / metabolism
  • Herbicides / administration & dosage
  • Herbicides / toxicity*
  • Homeostasis / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Oncorhynchus mykiss / metabolism
  • Oxidative Stress / drug effects
  • Testosterone / blood
  • Vitellogenins / blood
  • Vitellogenins / drug effects

Substances

  • Endocrine Disruptors
  • Herbicides
  • Vitellogenins
  • Testosterone
  • Estradiol
  • Catalase
  • Aryl Hydrocarbon Hydroxylases
  • Glutathione S-Transferase pi
  • Atrazine