Inhibition of Cholinesterase Enzymes Following a Single Dermal Dose of Chlorpyrifos and Methyl Parathion, Alone and in Combination, in Pregnant Rats

Abstract

Pregnant Sprague-Dawley rats (14-18 d of gestation) were treated with either a single dermal subclinical dose of 30 mg/kg (15% of dermal LD50) chlorpyrifos (O,O-diethyl-O-[3,5,6-trichloro-2-pyridinyl] phosphorothioate) or a single dermal subclinical dose of 10 mg/kg (15% of dermal LD50) methyl parathion (O,O-dimethyl O-4-nitrophenyl phosphorothioate) or the two in combination. Chlorpyrifos inhibited maternal and fetal brain acetylcholinesterase (AChE) activity within 24 h of dosing, (48% and 67% of control activity, respectively). Following application of methyl parathion, peak inhibition of maternal and fetal brain AChE activity occurred at 48 h and 24 h after dosing (17% and 48% of control activity, respectively). A combination of chlorpyrifos and methyl parathion produced peak inhibition of maternal and fetal brain AChE activity at 24 h postdosing (35% and 73% of control activity, respectively). Maternal and fetal brain AChE activity recovered to various degrees of percentage of control 96 h after dosing. Application of methyl parathion or chlorpyrifos alone or in combination significantly inhibited maternal plasma butyrylcholinesterase (BuChE) activity. No significant inhibition of fetal plasma BuChE activity was detected. Peak inhibition of maternal liver BuChE occurred 24 h after application of methyl parathion or chlorpyrifos alone or in combination (64%, 80%, and 61% of control activity, respectively). Significant inhibition of placental AChE occurred within 24 h after application of methyl parathion or chlorpyrifos alone or in combination. The results suggest that methyl parathion and chlorpyrifos, alone or in combination, were rapidly distributed in maternal and fetal tissues, resulting in rapid inhibition of cholinesterase enzyme activities. The lower inhibitory effect of the combination could be due to competition between chlorpyrifos and methyl parathion for cytochrome P-450 enzymes, resulting in inhibition of the formation of the potent cholinesterase inhibitor oxon forms. The faster recovery of fetal plasma BuChE is attributed to the de novo synthesis of cholinesterase by fetal tissues compared to maternal tissues.

Maternal exposure to nicotine and chlorpyrifos, alone and in combination, leads to persistently elevated expression of glial fibrillary acidic protein in the cerebellum of the offspring in late puberty

“…Male offspring from mothers treated with either chlorpyrifos or nicotine alone showed a significant increase in AChE activity in the brainstem while female offspring from mothers treated with either nicotine or a combination of nicotine and chlorpyrifos showed a significant increase ($134 and 126% of control, respectively) in AChE activity in the brainstem. Maternal exposure to high doses of chlorpyrifos to developing fetus or pups produced inhibition of AChE in the maternal as well as the fetal (developing) rat (Lassiter et al 1998a(Lassiter et al , 1998b(Lassiter et al , 1999Abu-Qare et al 2001;Ashry et al 2002). The real-life exposure dose of chlorpyrifos in the present study is too small to produce any significant inhibitory effect on AChE.…”

The effect of consequent exposure of stress and dermal application of low doses of chlorpyrifos on the expression of glial fibrillary acidic protein in the hippocampus of adult mice

“…Individuals with histories of exposure to low, sub-clinical levels of chlorpyrifos have also reported reduced levels of concentration, word finding and short-term-memory impairment [5]. CPF has also been reported to produce neurobehavioral and morphological damages in the nervous systems of animals during embryonic life through to postnatal development [6,7]. Previous work by the authors has found that sub-toxic doses (1/5th and 1/2 LD 50 ) of chlorpyrifos applied dermally for 3 weeks can produce significant hippocampal neuronal loss, and that stress can exacerbate this damage [8].…”

Plasma, erythrocyte membrane bound enzymes and tissue histopathology in male Wistar rats exposed to common insecticides

“…25) Treatment with of dichlorvos and lambda-cyhalothrin resulted in a statistically significant decrease in acetyl cholinesterase activity in each case; the inhibition of acetylcholinesterase activity might be due to direct interaction of the pesticide with enzymes. 26) Glucose-6-phosphate dehydrogenase is an important enzyme of the hexose monophosphate shunt; its functions in mature red blood cells (erythrocytes) is to generate NADPH, which is required for the conversion of oxidized glutathione (GSSG) to GSH, thus protecting the cell from oxidative damage, which, in turn, is necessary for the membrane integrity of erythrocyte membranes. 27) This might be the reason for the increased fragility of erythrocytes upon treatment with different pesticides.…”