Inhibition of Hepatic Xenobiotic Metabolism and of Glutathione‐Dependent Enzyme Activities by Zinc Ethylene‐Bis‐Dithiocarbamate in the Rabbit *

Abstract

Effects of either a single (300 mg/kg) or a subchronic (0.3 and 0.6% for 70 days) oral administration of a dithiocarbamate fungicide (zinc ethylene-bis-dithiocarbamate, zineb) on hepatic drug metabolism and on the activity of several glutathione-dependent enzymes were investigated in male New Zealand White rabbits. While a pronounced reduction in the rate of oxidative biotransformations occurred after either single or repeated exposure, both cytochrome P450 and total haem content were lowered following acute challenge to zineb. None of the experimental protocols affected microsomal carboxylesterase but induced a marked increase in glutathione content and none of the examined glutathione-dependent enzymes was altered by the single administration of zineb, whereas the subchronically exposed rabbits showed a fall in the activities of both total glutathione S-transferase and selenium-independent glutathione peroxidase. In the 0.6% treated animals, a decrease in class mu glutathione S-transferase and glyoxalase I, and an increase in thiol-transferase activities were also recorded. It is concluded that (1) zineb is able to selectively impair oxidative drug metabolism with possible different mechanism(s) according to the duration of the exposure, (2) only the subchronic treatment affects glutathione-dependent enzymes, (3) the decrease in glutathione S-transferase activity would seem to be ascribed to a direct interaction with the fungicide.

Characterization of xenobiotic metabolizing enzymes in bovine small intestinal mucosa

“…, 1974) using the following substrates: 1‐chloro, 2,4‐dinitrobenzene (CDNB) (nonspecific substrate), 3,4‐dichloronitrobenzene (DCNB) for GSTμ, and ethacrinic acid for GSTπ. Selenium‐independent glutathione peroxidase activity, also referred to as GSTα, was measured using cumene hydroperoxide as substrate following the method by Nebbia et al. (1993).…”

Toxicity interaction between chlorpyrifos, mancozeb and soil moisture to the terrestrial isopod Porcellionides pruinosus

“…Treatments indicated by asterisks are significantly different from control (two-way ANOVA followed by Dunnett's post hoc test, α = 0.05). general impairment in organisms condition since this compound is still known to induce several non-specific responses such as oxidative stress (Tsang and Trombetta, 2007) and impairments on phases I and II of organisms' detoxification systems (Lewerenz and Plass, 1984;Szépvölgyi et al, 1989;Siddiqui et al, 1991;Nebbia et al, 1993). Besides, indirect effects related to the fungicidal effects of MCZ may also have been involved.…”

Joint effects of chlorpyrifos and mancozeb on the terrestrial isopod Porcellionides pruinosus: A multiple biomarker approach

“…However, MCZ was previously reported to inactivate phase I's cytochrome P450 enzymes (Szépvölgyi et al ; Siddiqui et al ), which in combination with GST inhibition is likely to constitute a serious impairment in overall detoxification capacity. Nebbia et al () showed that the action of zineb (another Zn 2+ ‐containing dithiocarbamate fungicide) affects mixed‐function oxidases, even before acting on the glutathione‐related enzymes, which highlights the generalized impairments on multiple detoxification mechanisms. Pesticide biotransformation by organisms can be an important process for promoting interaction among pesticides (Spurgeon et al ).…”