Developmental changes in drug-metabolizing enzyme expression during metamorphosis of Xenopus tropicalis

J Toxicol Sci. 2017;42(5):605-613. doi: 10.2131/jts.42.605.

Abstract

A large number of chemicals are routinely detected in aquatic environments, and these chemicals may adversely affect aquatic organisms. Accurate risk assessment requires understanding drug-metabolizing systems in aquatic organisms because metabolism of these chemicals is a critical determinant of chemical bioaccumulation and related toxicity. In this study, we evaluated mRNA expression levels of nuclear receptors and drug-metabolizing enzymes as well as cytochrome P450 (CYP) activities in pro-metamorphic tadpoles, froglets, and adult frogs to determine how drug-metabolizing systems are altered at different life stages. We found that drug-metabolizing systems in tadpoles were entirely immature, and therefore, tadpoles appeared to be more susceptible to chemicals compared with metamorphosed frogs. On the other hand, cyp1a mRNA expression and CYP1A-like activity were higher in tadpoles. We found that thyroid hormone (TH), which increases during metamorphosis, induced CYP1A-like activity. Because endogenous TH concentration is significantly increased during metamorphosis, endogenous TH would induce CYP1A-like activity in tadpoles.

Keywords: Cytochrome P450; Drug-metabolizing enzyme; Metamorphosis; Thyroid hormone; Xenopus tropicalis.

MeSH terms

  • Animals
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Gene Expression / genetics*
  • Gene Expression Regulation, Developmental / genetics*
  • Metamorphosis, Biological / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Thyroid Hormones / metabolism*
  • Thyroid Hormones / physiology*
  • Xenopus / genetics*
  • Xenopus / physiology*

Substances

  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Thyroid Hormones
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP1A1