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Comparative neurochemical effects of repeated methyl parathion or chlorpyrifos exposures in neonatal and adult rats.
Toxicol Appl Pharmacol. 1999 Jul 15; 158(2):186-96.TA

Abstract

Several studies have reported higher sensitivity based on lethality in young animals compared to adults following acute exposure to organophosphorus insecticides (OPs). We propose that age-related differences in sensitivity to OPs may differ qualitatively and quantitatively with different OPs and varying exposure conditions (e. g., high vs. low dose, acute vs. repeated). To test this hypothesis, we treated neonatal (7 days of age) and adult (90 days of age) rats with either methyl parathion (MPS) or chlorpyrifos (CPF) daily for 14 days and measured neurochemical endpoints {cholinesterase (ChE) inhibition, total muscarinic receptor ([(3)H]quinuclidinyl benzilate, QNB) and muscarinic M2 subtype-preferential ([(3)H]AF-DX 384) binding} in frontal cortex and striatum at timepoints both during (1 day after the 7(th) and 14(th) dose) and after (8 days after the 14(th) dose) exposures. Repeated CPF exposures were associated with relatively similar degrees of ChE inhibition between the age groups during dosing but more extensive inhibition was noted in adults after termination of exposures. Relatively similar changes in muscarinic receptor binding were also noted between age groups following CPF exposures. Moreover, the degree of muscarinic receptor binding reduction relative to ChE inhibition appeared similar in both age groups following CPF exposures. In contrast, ChE activity and muscarinic receptor binding were generally more reduced in neonatal relative to adult brain regions following repeated MPS exposures. Furthermore, the relationship between the degree of ChE inhibition and the reduction in cortical muscarinic receptor binding appeared different between the age groups, i.e., more extensive reduction was noted in neonates compared to adults with a given level of ChE inhibition. We conclude that OP-selective differences in in vivo ChE sensitivity, differential rates of enzyme recovery following inhibition, and age-dependent differences in muscarinic receptor adaptations can all influence the nature of age-related susceptibility to OPs.

Authors+Show Affiliations

College of Pharmacy and Health Sciences, Northeast Louisiana University, Monroe, Louisiana, 71209, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10406933

Citation

Liu, J, et al. "Comparative Neurochemical Effects of Repeated Methyl Parathion or Chlorpyrifos Exposures in Neonatal and Adult Rats." Toxicology and Applied Pharmacology, vol. 158, no. 2, 1999, pp. 186-96.
Liu J, Olivier K, Pope CN. Comparative neurochemical effects of repeated methyl parathion or chlorpyrifos exposures in neonatal and adult rats. Toxicol Appl Pharmacol. 1999;158(2):186-96.
Liu, J., Olivier, K., & Pope, C. N. (1999). Comparative neurochemical effects of repeated methyl parathion or chlorpyrifos exposures in neonatal and adult rats. Toxicology and Applied Pharmacology, 158(2), 186-96.
Liu J, Olivier K, Pope CN. Comparative Neurochemical Effects of Repeated Methyl Parathion or Chlorpyrifos Exposures in Neonatal and Adult Rats. Toxicol Appl Pharmacol. 1999 Jul 15;158(2):186-96. PubMed PMID: 10406933.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative neurochemical effects of repeated methyl parathion or chlorpyrifos exposures in neonatal and adult rats. AU - Liu,J, AU - Olivier,K, AU - Pope,C N, PY - 1999/7/17/pubmed PY - 1999/7/17/medline PY - 1999/7/17/entrez SP - 186 EP - 96 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 158 IS - 2 N2 - Several studies have reported higher sensitivity based on lethality in young animals compared to adults following acute exposure to organophosphorus insecticides (OPs). We propose that age-related differences in sensitivity to OPs may differ qualitatively and quantitatively with different OPs and varying exposure conditions (e. g., high vs. low dose, acute vs. repeated). To test this hypothesis, we treated neonatal (7 days of age) and adult (90 days of age) rats with either methyl parathion (MPS) or chlorpyrifos (CPF) daily for 14 days and measured neurochemical endpoints {cholinesterase (ChE) inhibition, total muscarinic receptor ([(3)H]quinuclidinyl benzilate, QNB) and muscarinic M2 subtype-preferential ([(3)H]AF-DX 384) binding} in frontal cortex and striatum at timepoints both during (1 day after the 7(th) and 14(th) dose) and after (8 days after the 14(th) dose) exposures. Repeated CPF exposures were associated with relatively similar degrees of ChE inhibition between the age groups during dosing but more extensive inhibition was noted in adults after termination of exposures. Relatively similar changes in muscarinic receptor binding were also noted between age groups following CPF exposures. Moreover, the degree of muscarinic receptor binding reduction relative to ChE inhibition appeared similar in both age groups following CPF exposures. In contrast, ChE activity and muscarinic receptor binding were generally more reduced in neonatal relative to adult brain regions following repeated MPS exposures. Furthermore, the relationship between the degree of ChE inhibition and the reduction in cortical muscarinic receptor binding appeared different between the age groups, i.e., more extensive reduction was noted in neonates compared to adults with a given level of ChE inhibition. We conclude that OP-selective differences in in vivo ChE sensitivity, differential rates of enzyme recovery following inhibition, and age-dependent differences in muscarinic receptor adaptations can all influence the nature of age-related susceptibility to OPs. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/10406933/Comparative_neurochemical_effects_of_repeated_methyl_parathion_or_chlorpyrifos_exposures_in_neonatal_and_adult_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(99)98693-3 DB - PRIME DP - Unbound Medicine ER -