Effect of mancozeb on hydrolytic metabolism of xenobiotics.

The present investigation reports the effect of chronic oral administration of mancozeb, a fungicide, on hepatic microsomal carboxylesterases/amidases or B-esterases responsible for hydrolytic metabolism of aspirin (acetylsalicylic acid or ASA) at pH 5.5 and 7.4, 2-acetylaminofluorene (AAF), acetanilide and p-nitrophenylacetate (NPA) and cholinesterase in rat. Oral administration of mancozeb (250 mg/kg/day) for 30 days caused significant stimulation of ASA esterase I (pH 5.5), ASA esterase II (pH 7.4), AAF N-deacetylase and acetanilide N-deacetylase in liver. However, the activities of NPA esterase and cholinesterase remained unaffected. Evaluation of induction kinetics demonstrated that the pattern and magnitude of responses of these microsomal hydrolases to mancozeb treatment for 7 days were comparable to those obtained after treatment for 30 days. The activities of hydrolases were not altered in animals killed 4 hr after an oral dose of mancozeb. Mancozeb did not affect these hydrolases in vitro.