Effects of the fungicide prochloraz on xenobiotic metabolism in rainbow trout: inhibition in vitro and time course of induction in vivo

Abstract

1. Interactions between the fungicide prochloraz and the hepatic cytochrome P-450 of rainbow trout were studied by determination of enzymic activities in vitro using the microsomal fraction, and by kinetic studies. 2. Prochloraz inhibited 7-ethoxyresorufin-O-deethylase (EROD) in vitro. This inhibition was partially non-competitive: the enzyme-substrate-inhibitor (ESI) complex was catalytically active (68% of the activity of the enzyme-substrate complex). 3. Prochloraz in vitro inhibited aldrin epoxidase (AE) by a linear mixed-type mechanism. This inhibition might be high because of high affinity for prochloraz and lack of catalytic activity of the ESI complex. 4. Effects of prochloraz in vivo were studied as a function of time after intraperitoneal injection. Total cytochrome P-450 increased for more than 21 days. 5. EROD increased slightly at day 4 and then returned to control level. Kinetics showed an increase in apparent Km and Vmax. AE was strongly inhibited at day 4 (large increase in apparent Km) and then returned to control level in 21 days. 6. Spectral interactions with aniline showed strong inhibition and recovery to an activated level at day 21.

Quantifying Synergy: A Systematic Review of Mixture Toxicity Studies within Environmental Toxicology

“…Azole fungicides have, for example, shown to give protective effects against pyrethroid toxicity at low doses in bees [52] and the aquatic invertebrate Daphnia magna (pers.obs. ), and have been shown to induce synergy together with organophosphates in birds pre-treated with prochloraz [74]–[76]. In the bird studies increased metabolism of the organophosphates was measured, strongly indicating P450 induction [75], [76].…”

Modulation of CYP1A expression in rainbow trout by a technical grade formulation of propiconazole

“…Prochloraz caused a concentrationdependent inhibition of ovarian microsomal aromatase activity and follicular oestradiol secretion in rainbow trout [44]. Prochloraz and clotrimazole have also been shown to inhibit cytochrome P450‐mediated xenobiotic metabolism in rainbow trout [16] and gizzard shad [37], respectively. Because propiconazole interacts with cytochrome P450 in a similar way as other antifungal imidazole compounds, propiconazole and/ or unidentified compounds within the TGP have the potential to modulate a wide range of cytochrome P450‐dependent processes in wildlife.…”

DEMETHYLATION OF THE PESTICIDE METHOXYCHLOR IN LIVER AND INTESTINE FROM UNTREATED, METHOXYCHLOR-TREATED, AND 3-METHYLCHOLANTHRENE-TREATED CHANNEL CATFISH (ICTALURUS PUNCTATUS): EVIDENCE FOR ROLES OF CYP1 AND CYP3A FAMILY ISOZYMES

“…As well as CYP1 family inducers, such as polyaromatic hydrocarbons and polychlorinated biphenyls, fish may be exposed to a variety of agricultural chemicals, some of which interact with P450 and may affect methoxychlor biotransformation. Imidazole and triazole-containing agrochemicals such as prochloraz, propiconazole, and thiobendazole interact with P450 acutely to inhibit monooxygenation (Snegaroff and Bach, 1989), similarly to the antifungal drugs ketoconazole and clotrimazole, although there is evidence that chronic exposure to azoles induces P450 in fish (Egaas et al, 1999;Hegelund et al, 2004). This research aims to create a better understanding of the demethylation of methoxychlor in channel catfish and subsequently the factors creating the endocrine-disrupting toxicity of methoxychlor.…”