Tags

Type your tag names separated by a space and hit enter

Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism.
Toxicol Appl Pharmacol. 1997 Dec; 147(2):411-8.TA

Abstract

Juvenile rats are more susceptible to the acute toxicity of the phosphorothionate insecticides parathion and chlorpyrifos than are adult rats. Developmental changes in brain acetylcholinesterase and hepatic aliesterase (carboxylesterase), cytochrome P450, and the P450-mediated metabolism of these two phosphorothionate insecticides were investigated in male Sprague-Dawley rats. Specific activities of acetylcholinesterase in cerebral cortex, but not medulla oblongata, and of liver aliesterases increased with age, indicating the presence of both more target esterases and more protective esterases, respectively, in the adult compared to the juvenile animal. Sensitivity of the brain acetylcholinesterase to inhibition by paraoxon and chlorpyrifosoxon, as measured by IC50 values, did not change significantly with age, whereas the hepatic aliesterase sensitivity to inhibition decreased with age. Progressive increases in activities of P450-mediated activation (desulfuration) (6- to 14-fold) and detoxication (dearylation) (2- to 4-fold), as well as concentrations of P450 (7-fold) and protein (2-fold), were observed between neonate and adult hepatic microsomes. Microsomal pentoxyresorufin O-dealkylase activity followed a developmental pattern similar to desulfuration and dearylation, displaying a 16-fold increase between neonates and adults. However, microsomal ethoxyresorufin O-deethylase activity increased until 21 days of age, displaying a 16-fold increase, then decreased in adulthood to a level 10-fold higher than neonates. These results indicate that target enzyme sensitivity is not responsible for age-related toxicity differences, nor is the potential for hepatic bioactivation, whereas lower levels of hepatic aliesterase-mediated protection and P450-mediated dearylation probably contribute significantly to the greater sensitivity of juveniles to phosphorothionate toxicity.

Authors+Show Affiliations

Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University 39762-9825, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9439736

Citation

Atterberry, T T., et al. "Age-related Differences in Parathion and Chlorpyrifos Toxicity in Male Rats: Target and Nontarget Esterase Sensitivity and Cytochrome P450-mediated Metabolism." Toxicology and Applied Pharmacology, vol. 147, no. 2, 1997, pp. 411-8.
Atterberry TT, Burnett WT, Chambers JE. Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism. Toxicol Appl Pharmacol. 1997;147(2):411-8.
Atterberry, T. T., Burnett, W. T., & Chambers, J. E. (1997). Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism. Toxicology and Applied Pharmacology, 147(2), 411-8.
Atterberry TT, Burnett WT, Chambers JE. Age-related Differences in Parathion and Chlorpyrifos Toxicity in Male Rats: Target and Nontarget Esterase Sensitivity and Cytochrome P450-mediated Metabolism. Toxicol Appl Pharmacol. 1997;147(2):411-8. PubMed PMID: 9439736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism. AU - Atterberry,T T, AU - Burnett,W T, AU - Chambers,J E, PY - 1998/1/24/pubmed PY - 1998/1/24/medline PY - 1998/1/24/entrez SP - 411 EP - 8 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 147 IS - 2 N2 - Juvenile rats are more susceptible to the acute toxicity of the phosphorothionate insecticides parathion and chlorpyrifos than are adult rats. Developmental changes in brain acetylcholinesterase and hepatic aliesterase (carboxylesterase), cytochrome P450, and the P450-mediated metabolism of these two phosphorothionate insecticides were investigated in male Sprague-Dawley rats. Specific activities of acetylcholinesterase in cerebral cortex, but not medulla oblongata, and of liver aliesterases increased with age, indicating the presence of both more target esterases and more protective esterases, respectively, in the adult compared to the juvenile animal. Sensitivity of the brain acetylcholinesterase to inhibition by paraoxon and chlorpyrifosoxon, as measured by IC50 values, did not change significantly with age, whereas the hepatic aliesterase sensitivity to inhibition decreased with age. Progressive increases in activities of P450-mediated activation (desulfuration) (6- to 14-fold) and detoxication (dearylation) (2- to 4-fold), as well as concentrations of P450 (7-fold) and protein (2-fold), were observed between neonate and adult hepatic microsomes. Microsomal pentoxyresorufin O-dealkylase activity followed a developmental pattern similar to desulfuration and dearylation, displaying a 16-fold increase between neonates and adults. However, microsomal ethoxyresorufin O-deethylase activity increased until 21 days of age, displaying a 16-fold increase, then decreased in adulthood to a level 10-fold higher than neonates. These results indicate that target enzyme sensitivity is not responsible for age-related toxicity differences, nor is the potential for hepatic bioactivation, whereas lower levels of hepatic aliesterase-mediated protection and P450-mediated dearylation probably contribute significantly to the greater sensitivity of juveniles to phosphorothionate toxicity. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/9439736/Age_related_differences_in_parathion_and_chlorpyrifos_toxicity_in_male_rats:_target_and_nontarget_esterase_sensitivity_and_cytochrome_P450_mediated_metabolism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(97)98303-4 DB - PRIME DP - Unbound Medicine ER -