comparative study of inhibition of brain and plasma cholinesterase and hepatic and plasma aliesterases in young and adult rats following exposures to three organophosphorothionate insecticides

ABSTRACT

Young rats are more sensitive than adults to a variety of Organophosphorothionate insecticides [OPS], compounds which act in vivo by inhibition of Cholinesterase and aliesterases. Little is known, however, regarding age-related differences in biochemical responses to these toxicants. The time course of Cholinesterase and aliesterases inhibit and recovery in different tissues were compared in young [14 days of age] and adult [90-100 days of -age] rats after treatment with high sublethal intraperitoneal dosages of parathion, methyl parathion or chlorpyrifos. Young rats were more sensitive than adult in all cases [high sublethal doses for parathion, methyl parathion and chlorpyrifos; young = 0.5, 5 and 10 mg/kg, i.p.; adult = 4, 12 and 60 mg/kg, i.p... respectively]. In general, the maximal inhibition of brain regions and plasma Cholinesterase activity was not immediate with parathion and chlorpyrifos, in young and adult rats, reflecting the time required for bioactivation of the phosphorothionates as well as the effectiveness of the aliesterases to inactive much of the hepatically generated oxons. In contrast, brain regions and plasma Cholinesterase activities were rapidly inhibited following administration of methyl parathion in both age groups reflecting the low sensitivity of the aliesterases to methyl paraoxon. In general, maximal plasma and brain regions Cholinesterase inhibition was similar [greater than 80 percent] in both age groups but Cholinesterase activity recovered faster in young rats. Aliesterases were inhibited to a greater extent than acetyl cholinesterase at each sampling time with parathion and chlorpyrifos in young and adult rats where the reverse was true with methyl parathion .The very prolonged inhibition of esterase activities following chlorpyrifos treatment probably results from its substantially greater lipophilicity compared to the other compouritls, which would allow it to be stored and released for gradual bioactivation The data reported indicate that young rats are more sensitive to sublethal dosages from these compounds and that high sublethal doses exposure produce extensive plasma and different brain regions cholinesterase and plasma and liver aliesterases inhibition in both age groups. Significant inhibitor- related and age-related differences in the duration of cholinesterase and aliesterases inhibition can ensue, however, following such Organophosphorothionate insecticides exposures. Additionally, under defined experimental conditions plasma cholinesterase inhibition may be a useful quantitative index for the degree of brain cholinesterase inhibition following organophosphorous exposures