Effects of tebuconazole on cytochrome P450 enzymes, oxidative stress, and endocrine disruption in male rats

Jr Di Yang, Shing Hwa Liu, Mei Hsiu Liao, Ruei Ming Chen, Pei Yu Liu, Tzuu Huei Ueng

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The major objective of the present study was to determine the ability of a triazole fungicide tebuconazole to induce cytochrome P450-dependent monooxygenases, oxidative stress, and endocrine-disrupting activity using male rats treated with tebuconazole at 10, 25, and 50 mg/kg p.o. once daily for 28 days. In liver, tebuconazole dose-dependently increased microsomal contents of cytochrome P450 and cytochrome b5 and the activities of NADPH-cytochrome P450 reductase, 7-ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, pentoxyresorufin O-dealkylase, 7-ethoxycoumarin O-deethylase, aniline hydroxylase, and erythromycin N-demethylase. In kidney, tebuconazole increased 7-ethoxycoumarin O-deethylase activity without affecting other monooxygenase activities. In marked contrast to liver and kidney, tebuconazole decreased testicular 7-ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, 7-ethoxycoumarin O-deethylase, aniline hydroxylase, and erythromycin N-demethylase activities. The results of immunoblot analysis of liver microsomes of controls and tebuconazole-treated rats revealed that tebuconazole induced CYP1A1/2, CYP2B1/2, CYP2E1, and CYP3A proteins in liver. Additions of tebuconazole to liver microsomes inhibited microsomal 7-ethoxycoumarin O-deethylase activity in vitro (IC50 = 1.50–1.69 µM). Treatment of rats with tebuconazole decreased glutathione content and increased glutathione S-transferase, superoxide dismutase, catalase, and glutathione peroxidase activities in liver; increased superoxide dismutase activities in kidney and testis; but decreased glutathione S-transferase activity in testis. Treatments with tebuconazole decreased serum testosterone concentration and cauda epididymal sperm count. The present study demonstrates that tebuconazole induces a multiplicity of CYPs and oxidative stress in liver; inhibits testicular P450 and glutathione S-transferase activities; and produces anti-androgenic effects in male rats.

Original languageEnglish
Pages (from-to)899-907
Number of pages9
JournalEnvironmental Toxicology
Volume33
Issue number8
DOIs
Publication statusPublished - Aug 1 2018

Fingerprint

Oxidative stress
Cytochrome P-450 Enzyme System
cytochrome
Rats
Oxidative Stress
enzyme
Liver
7-Alkoxycoumarin O-Dealkylase
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP1A1
Glutathione Transferase
Aniline Hydroxylase
Cytochrome P-450 CYP2B1
Liver Microsomes
Mixed Function Oxygenases
Kidney
Superoxide Dismutase
Testis
tebuconazole
effect

Keywords

  • cytochrome P450
  • endocrine disruption
  • induction
  • oxidative stress
  • tebuconazole

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

Cite this

Effects of tebuconazole on cytochrome P450 enzymes, oxidative stress, and endocrine disruption in male rats. / Yang, Jr Di; Liu, Shing Hwa; Liao, Mei Hsiu; Chen, Ruei Ming; Liu, Pei Yu; Ueng, Tzuu Huei.

In: Environmental Toxicology, Vol. 33, No. 8, 01.08.2018, p. 899-907.

Research output: Contribution to journalArticle

Yang, Jr Di ; Liu, Shing Hwa ; Liao, Mei Hsiu ; Chen, Ruei Ming ; Liu, Pei Yu ; Ueng, Tzuu Huei. / Effects of tebuconazole on cytochrome P450 enzymes, oxidative stress, and endocrine disruption in male rats. In: Environmental Toxicology. 2018 ; Vol. 33, No. 8. pp. 899-907.
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