A comparative study of blood changes and brain acetylcholinesterase inhibition by monocrotophos and its analogues in rats.
The effects of monocrotophos and its newly synthesized analogues, RPR-II and RPR-V, on hematology and blood chemistry 24 hr post-treatment were studied in rats given doses of 0.96, 1.23, and 3.0 mg/kg po, respectively. It was found that monocrotophos caused a significant increase in the mean WBC count. RPR-V, a significant decrease in hematocrit and RBC count, whereas RPR-II did not alter any hematological parameter. The activities of membrane-bound enzymes in serum were not significantly changed by all three compounds except for a statistically significant increase of 38% in SGOT activity by RPR-II. Only monocrotophos caused a significant inhibition of the brain acetylcholinesterase activity. In vitro studies with partially purified preparations of rat brain cholinesterase revealed that monocrotophos was the most potent anticholinesterase agent, followed by RPR-II and RPR-V. All three compounds caused inhibition of rat brain cholinesterase by decreasing the Vmax and increasing the Km values, indicating a mixed type of inhibition. The two analogues appeared to be less neurotoxic than monocrotophos.
Siddiqui
M K
MK
Biology Group, Indian Institute of Chemical Technology, Hyderabad.
Rahman
M F
MF
Mustafa
M
M
Rahman
M F
MF
Bhalerao
U T
UT
D000110:Acetylcholinesterase / Q000378:metabolism*; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001921:Brain / Q000201:enzymology*; D002800:Cholinesterase Inhibitors; D004305:Dose-Response Relationship, Drug; D004906:Erythrocyte Count / Q000187:drug effects*; D006400:Hematocrit; D007700:Kinetics; D007958:Leukocyte Count / Q000187:drug effects*; D008297:Male; D008999:Monocrotophos / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002800:Cholinesterase Inhibitors; D008999:Monocrotophos; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000110:Acetylcholinesterase; D000469:Alkaline Phosphatase