Inhibition and recovery of maternal and fetal cholinesterase enzymes following a single oral dose of chlorpyrifos in rats.
Pregnant Sprague-Dawley rats (14-18 days of gestation) were treated with a single dose of 50 mg/kg (61% of oral LD50 in female rats) of chlorpyrifos ( 0,0-diethyl- 0-3,5,6-trichloro-2-pyridyl phosphorothioate) by oral gavage. Animals treated on day 18 of gestation were sacrificed at 1, 2, 4, 12 h after dosing. Animals treated on days 17, 16, 15, and 14 of gestation were sacrificed at 24, 48, 72, and 96 h after dosing, respectively. Maternal and fetal brain acetylcholinesterase (AchE) and plasma butyrylcholinesterase (BuChE) activities were significantly inhibited 1 h after treatment. Activity of fetal brain AChE and plasma BuChE recovered faster than that of the maternal enzymes. Peak inhibition of maternal spinal cord AChE and BuChE activities occurred 2 h and 1 h after dosing, respectively. Maternal spinal cord BuChE activity was totally recovered by 96 h compared to the partial recovery of spinal cord AChE activity. Maternal liver BuChE activity was significantly decreased within 1 h of dosing. The individual molecular forms (10S and 4S) of maternal and fetal brain AChE and BuChE activities were significantly decreased 1 h after treatment. Recovery of both forms of fetal brain AChE activity was much faster than the maternal forms. Activity of the 10S form of maternal control brain AChE was significantly higher than in the fetus control. The rapid recovery of cholinesterase enzymes in the fetus is attributed to the de novo synthesis of AChE enzymes in the fetus compared to the mother.
Ashry
Khaled M
KM
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Abu-Qare
Aqel W
AW
Saleem
Fathy R
FR
Hussein
Yousef A
YA
Hamza
Salah M
SM
Kishk
Amal M
AM
Abou-Donia
Mohamed B
MB
D000110:Acetylcholinesterase / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism*; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000201:enzymology*; D007928:Lethal Dose 50; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology
D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D004390:Chlorpyrifos