Additive inhibitory action of chlorpyrifos and polycyclic aromatic hydrocarbons on acetylcholinesterase activity in vitro.
This study tested the hypothesis that the inhibition of acetylcholinesterase is greater when the insecticide chlorpyrifos (CPF) is in the presence of several polycyclic aromatic hydrocarbons (PAHs) found in house dust. CPF-oxon (CPFO) inhibition curves of purified AChE (electric eel) were generated in the presence or absence of different concentrations of the PAHs pyrene, benzo(a)pyrene, anthracene, and fluoranthene. Without CPF-oxon, all four PAHs themselves inhibited AChE activity with IC50 values in the range 8.2-17 microM. The IC50 for benzo(a)pyrene with human recombinant AChE was 1.5 microM. When AChE was incubated with CPF-oxon together with the PAHs, the inhibitory effect on AChE was additive. This was exemplified by large (60-80%) and significant (P<0.01) inhibition in AChE activity by the PAHs when combined with nanomolar concentrations of CPF-oxon. Kinetic studies indicated that benzo(a)pyrene inhibited AChE in a noncompetitive manner, and the reduction in maximal velocity (Vmax) by benzo(a)pyrene and CPFO together was the sum of the inhibitory effect of the two inhibitors alone, further supporting an additive effect. These data suggest that some PAHs have anticholinesterase activity, and contribute in an additive manner to the inhibitory effect of CPFO on AChE in vitro. Further research is needed to determine the toxicological relevance of these findings.
Jett
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DA
Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD 21205, USA. djett@jhsph.edu
Navoa
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RV
Lyons
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MA
D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D004390:Chlorpyrifos / Q000031:analogs & derivatives / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D004593:Electrophorus; D005449:Fluorenes / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology*
D000873:Anthracenes; D002273:Carcinogens; D002800:Cholinesterase Inhibitors; D005449:Fluorenes; D011084:Polycyclic Aromatic Hydrocarbons; D001564:Benzo(a)pyrene; C007738:fluoranthene; C009618:O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate; D000110:Acetylcholinesterase; C034020:anthracene; D004390:Chlorpyrifos