Heterogeneous effects of ethylenebisdithiocarbamate (EBDC) pesticides on oxidative metabolism of xenobiotics.
Comparative evaluation of the acute effects of ethylenebisdithiocarbamate (EBDC) fungicides, mancozeb and zineb on microsomal mixed function oxidases (MFO) revealed marked substrate-dependent inhibition of oxidative metabolism of aminopyrine, p-nitroanisole and aniline in rats sacrificed 4 hr after oral administration of 100 mg mancozeb or zineb/kg body weight. Mancozeb inhibited p-nitroanisole O-dealkylase and aniline hydroxylase to a greater degree than zineb, whereas the inhibition of aminopyrine N-demethylase by the two fungicides was quantitatively comparable. Interestingly, aryl hydrocarbon hydroxylase (AHH) which exhibited maximum inhibition with mancozeb, remained unaffected following zineb administration. The time-course and dose-dependence of MFO inhibition examined 1 and 4 hr after a single oral dose of 100 mg or 250 mg zineb/kg was expressed as a dose-dependent decline in the rate of xenobiotic biotransformation at 4 hr. In vitro interaction of zineb with MFO resulted in slightly greater inhibition of aminopyrine, p-nitroanisole and aniline while AHH exhibited more pronounced decrease with mancozeb. The magnitude of inhibition of aminopyrine N-demethylase and AHH was independent of the time of preincubation of fungicides with the enzyme. Kinetic studies indicated the non-competitive nature of AHH inhibition. Chronic oral treatment with mancozeb and zineb at a dose of 250 mg/kg for 4 weeks did not modify xenobiotic biotransformations except for a slight induction of aminopyrine N-demethylase by mancozeb.
Siddiqui
A
A
Industrial Toxicology Research Centre, Lucknow, India.
Ali
B
B
Srivastava
S P
SP
D000818:Animals; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008344:Maneb / Q000633:toxicity*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D010575:Pesticides / Q000633:toxicity*; D051381:Rats; D015262:Xenobiotics / Q000378:metabolism*; D015038:Zineb / Q000633:toxicity*
D010575:Pesticides; D015262:Xenobiotics; D008344:Maneb; D006899:Mixed Function Oxygenases; C013099:mancozeb; D015038:Zineb