Cholinesterase activities during acute and sub-acute phosphamidon treatments in rats

Abstract

Organophosphate pesticides exert their toxic effects by cholinesterase inhibition and the consequent prolongation of the undesirable effects of accumulation of acetylcholine. However, as time elapses, sustained cholinesterase inhibition through sustained sub-acute administration of organophosphates leads to the gradual disappearance of initial signs of toxicity, termed behavioral tolerance. In the present study, cholinesterase activities in different regions of rat brain were examined upon the administration of acute and sub-acute doses of the organophosphate phosphamidon. Separate groups of male albino rats were given a one-time acute dose of 1/2 LD₅₀ (6.64 mg/kg body wt/day), and a daily sub-acute oral dose of phosphamidon (4.333 mg, equivalent to 1/3 of LD₅₀) for 15 days. The activities of acetylcholinesterase (AChE), erythrocyte cholinesterase (EChE) and plasma cholinesterase (PChE) were estimated in both control and experimental groups. Activities of all the cholinesterases showed a decrease, and the decrease varied among different brain regions at different times. Maximal decrease under acute and sub-acute administrations was recorded from striatum. Greater inhibition of AChE and PChE activities was observed in 1 day after sub-acute administration, while EChE activity recorded highest decrease in 15 days of sub-acute administration. Recovery towards the controls under sub-acute dosing was observed with time for AChE and PChE but not for EChE. After 7 days, disappearance of majority of the signs and symptoms of toxicity was noticed as in our other studies, while the reduction in cholinesterase activities was found up to the 15th day, indicating the development of behavioral tolerance to phosphamidon. Pseudocholinesterase activities seem to have a role in regulating homeostasis of cholinesterases and in the development of symptomatic tolerance to phosphamidon.

Keywords/phrases: Cholinesterases, Erythrocytes, Phosphamidon, Plasma Rat brain, Tolerance

Ethiop. J. Biol. Sci., 8(2): 99-108, 2009