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

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 b 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 (IC = 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.

Ecotoxicological assessment of Uruguay River and affluents pre- and post-pesticides’ application using Caenorhabditis elegans for biomonitoring

“…Tebuconazole is a fungicide that has been frequently detected in agriculture systems at concentrations that affect endocrine function in organisms. For instance, it has been found to cause oxidative stress and endocrine disruption in rats (Yang et al 2018) and developmental toxicity associated to thyroid dysfunction in zebrafish (Li et al 2020). Finally, imazethapyr has also been reported by causing metabolic alterations in Cyprinus carpio (Moraes et al 2011), genotoxicity in tadpoles of Rhinella arenarum and Hypsiboas pulchellus species (Carvalho et al 2019;Perez-Iglesias et al 2017;Perez-Iglesias et al 2015), and also in mammalian cells (Soloneski et al 2017); however, the toxicity of herbicide is poorly characterized and needs to be further investigated.…”

Transgenerational reproductive and developmental toxicity of tebuconazole in Caenorhabditis elegans

“…TEB has been considered an endocrine‐disrupting chemical ,it could affect the reproduction and development of offspring in utero and increase the anogenital distance of female offspring (Taxvig et al, ). Previous studies demonstrated that TEB could produce anti‐androgenic effects in adult male rats with reduced serum testosterone level and sperm number (Yang et al, b). Common features of the azole fungicides epoxiconazole, prochloraz, and TEB were that they increased gestational length in dams, virilized female pups, and affected steroid hormone levels in fetuses and dams (Vinggaard, Nellemann, Dalgaard, Jørgensen, & Andersen, ; Vinggaard et al, ).…”

More than additive effects on liver triglyceride accumulation by combinations of steatotic and non-steatotic pesticides in HepaRG cells

“…To the best of our knowledge, the impact of FDO on CYP1A1 and CYP1A2 expression and EROD activity has not been shown before, but it was shown by Wetmore et al (2014) that FDO is mainly metabolized by CYP1A2. Effects of DIF, PPC and TBC on CYP1A1 and/or CYP1A2 expression or activity have been demonstrated previously (Egaas et al 1999;Knebel et al 2019b;Yang et al 2018;Zhang et al 2017). An increased metabolism of triazoles might be the underlying cause for enhanced steatotic effects, if not the parental triazole compounds, but their metabolites are the causative agents for steatosis.…”