In vitro kinetic characterization of inhibition of acetylcholinesterase by organophosphate and carbamate compounds in food animals

摘要

Organophosphate, dichlorvos (2,2-dichlorovinyldimethylphosphate, DDVP), and diazinon (DZN) as well as carbamates are currently found in contaminated water, dust, soil, agricultural waste, and elsewhere in the environment, and can be harmful after accidental or deliberate exposure. Intoxication by these compounds causes a generalized cholinergic crisis due to the inhibition of acetylcholinesterase (AChE), whose major physiological role in mammalian tissues is in nervous transmission. The half-maximal inhibitory concentration (IC_50) was found to be higher for carbaryl than DDVP and DZN, about 3-4 times in liver and about 4-6 times in muscles. The half time (t_(1/2)) of inhibition (8 μmol L~(-1) DDVP or DZN; 40μmol L~(-1) carbaryl) ranged between 4 and 16min and decreased as follows: pig > cattle > sheep for liver tissue, and cattle > sheep > pig for muscle. Rate constants of inhibition {k_i) ranged between 43 × 10~(-3) and 168 × 10~(-3)min~(-1) for liver and from 46 × KF~(-3) to 115 × 10~(-3)min~(-1) for muscles. Very little residual AChE activity (<6.1%) was seen in liver, but more was seen in muscle (<17%).