Toxicological Sciences 58, 282-289 (2000)
Copyright © 2000 by the Society of Toxicology
Environmental Toxicology |
Carboxylesterase and A-Esterase Activities during Maturation and Aging: Relationship to the Toxicity of Chlorpyrifos and Parathion in Rats
Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71209
Chlorpyrifos (CPF) and parathion (PS), two common organophosphorus (OP) pesticides, exhibit higher acute toxicity in younger animals compared to adults. Maturational differences in detoxification via carboxylesterases (CEs) and A-esterases (AEs) have been suggested as contributors to the higher sensitivity of younger animals to OP toxicants. AEs (e.g., chlorpyrifos oxonase and paraoxonase) catalytically inactivate while CEs stoichiometrically eliminate OP anticholinesterases. While earlier studies have reported a relationship between the toxicity of some OP pesticides and the maturational profile of AEs and CEs, little information exists on the relative OP-toxicant sensitivity and detoxification capacities of aged animals. In the present study, we investigated the relationship between toxicity of CPF and PS and the activity of CEs and AEs in liver, plasma, and lung of neonatal (7 day), juvenile (21-day), adult (3-month), and aged (24-month) Sprague Dawley rats. CE sensitivity in vitro to chlopyrifos oxon and paraoxon was also evaluated across age groups. Neonatal and juvenile rats were more sensitive than adults to the acute lethality of both CPF and PS. Aged rats exhibited similar sensitivity to CPF but were markedly more sensitive than adults to PS. Levels of CEs and AEs in neonatal and juvenile rats were significantly lower than in adult tissues. Aged rats showed similar levels of AEs in all tissues and CEs in liver and lung, but plasma CE levels were significantly lower (50%) when compared to the adult rats. There were no significant age-related differences in in vitro sensitivity of CEs to either chlorpyrifos oxon or paraoxon in any tissues. In general, acute sensitivity (MTD) was highly correlated with age-related differences in both esterase activities across all 3 tissues with CPF, but only plasma carboxylesterase activity was highly correlated with sensitivity to parathion. The results suggest that both carboxylesterase and A-esterase activities can be correlated with acute sensitivity to CPF and PS, but that age-related differences in CE activity are probably more important in differential toxicity. Furthermore, plasma carboxylesterase activity may play a more pivotal role in the differential sensitivity to PS.
Key Words: organophosphate; age-related; chlorpyrifos oxonase; paraoxonase; PON1; detoxification; maturation; aging.
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