Toxicity Of Parathion In Rats Research Articles

Protective effect of physostigmine and neostigmine against acute toxicity of parathion in rats

The effects of physostigmine and neostigmine on the parathin induced toxicity were examined in adult female rats. Physostigmine (100 μg/kg, ip) or neostigmine (200 μg/kg, ip) inhibited acetylcholinesterase (AChE) and cholinesterase (ChE) activities in blood, brain and lung when the enzyme activity was measured 30 min after the treatment. At the doses of two carbamates equipotent on brain AChE, neostigmine showed greater inhibition on peripheral AChE/ChE. The enzyme activity returned to normal in 120 min following the carbamates except in the lung of rats treated with neostigmine. Carbamates administered 30 min prior to parathion (2 mg/kg) antagonized the inhibition of AChE/ChE by parathion when the enzyme activity was measured 2 hr following parathion. Neostigmine showed greater protective effect on peripheral AChE/ChE. The effect of either carbamate on AChE/ChE was not significant 2 hr beyond the parathion treatment. Carbamates decreased the mortality of rats challenged with a lethal dose of parathion (4 mg/kg, ip) either when treated alone or in combination with atropine (10 mg/kg, ip). Lethal action of paraoxon (1.5 mg/kg, ip), the active metabolite of parathion, was also decreased by the carbamate treatment indicating that the protection was not mediated by competitive inhibition of metabolic conversion of parathion to paraoxon. The results suggest that carbamylation of the active sites may not be the sole underlying mechanism of protection provided by the carbamates.

Cimetidine enhances and phenobarbital decreases parathion toxicity

Parathion toxicity has been attributed to its metabolic product paraoxon which is formed in the mammal liver through the multiple oxidase enzymes. These are induced by barbiturates and inhibited by SKF 525 A and cimetidine. We assessed the effects of these drugs on the acute toxicity of parathion in rats by measuring the rate of survival at 24 h after the administration of the oral LD50 of parathion to four groups of rats: control and pretreated with the aforementioned drugs. Additional rats of these groups were used to measure the capability of liver isolated microsomes to transform p-nitroanisole to p-nitrophenol. In the control and cimetidine groups we also measured the transformation of parathion to paraoxon and p-nitrophenol by the liver microsomes. Phenobarbital increased the survival 100% whereas cimetidine and SKF 525 A dramatically potentiated parathion toxicity. Phenobarbital increased the formation of p-nitrophenol but cimetidine and SKF-525 A produced the opposite effect. Paraoxon and p-nitrophenol from parathion were decreased by cimetidine. Our results strongly suggest that parathion itself is largely responsible of its toxicity and the inhibition of its metabolism is harmful rather than beneficial.

Influence of sex hormones on parathion toxicity in rats: antiacetylcholinesterase activity of parathion and paraoxon in plasma, erythrocytes, and brain.

Administration of parathion resulted in a greater inhibition of acetylcholinesterase (AChE) activity of plasma, erythrocytes, and brain in female rats than in male rats. No sex-related difference was observed in the antiacetylcholinesterase activity of paraoxon, an active metabolite of parathion. Gonadectomy increased the susceptibility of males but had no perceptible effect on females, resulting in comparable inhibition of AChE by parathion in both sexes. Administration of testosterone led to recovery from increased sensitivity to the antiacetylcholinesterase activity of parathion in castrated males and afforded partial protection to ovariectomized females. On the other hand, administration of estradiol further enhanced the enzyme inhibition by parathion in castrated males but had no significant effect on that in ovariectomized females. Alterations in the status of sex hormones did not affect the antiacetylcholinesterase activity of paraoxon in plasma and erythrocytes. However, inhibition of AChE activity by paraoxon was significantly higher in brains of gonadectomized rats than those of normal rats and the effect was reversible on administration of the respective sex hormones. The results indicate that testosterone plays an important role in determining parathion toxicity (as reflected by its antiacetylcholinesterase activity), probably by activating the oxidative cleavage of the insecticide into nontoxic metabolites.

A study of the effect of ovex on parathion toxicity in rats.

Oral administration (100 mg/kg) of the miticide ovex (p-chlorophenyl p-chlorobenzene-sulfonate) caused a decrease in the hexobarbital sleeping time of rats. Administration of this same dosage of ovex resulted in a significant decrease in the toxicity of orally administered parathion (100 mg/kg) to rats.The changes in rats noted in conjunction with the increased resistance to organophosphate toxicity in vivo were an increased liver size, an increased rate of in vitro α-naphthyl acetate hydrolysis by the 9000 × g liver supernatant.The hexane-extractable organophosphate detected in the liver of the ovex-pretreated rats was significantly lower than the hexane extractable organophosphate found in the liver of the control rats.

Modification of microsomal enzyme activity and parathion toxicity in rats

Compounds which alter hepatic microsomal enzyme activity may also affect the toxicity of organic phosphate insecticides (1,2). The effect of compounds such as SKF-525A (2-diethylaminoethyl 2,2diphenylvalerate-HCl), 3,4 Benzpyrene and phenobarbital on the in vitro metabolism of parathion by rat liver microsome~-ha~n reported by ~eal (3,4). Studies have also been carried out on the effect of phenobarbital (1,2), aldrin, chlordan and lindane (5) on the acute toxicity of parathion. IIowever, there has been no attempt to correlate in vitro parathion degradation with in vivo toxicolo~ca~----~ta in the above studies. I-~ suc--~--a correlation existed it would permit the use of in vitro assays to establish the effect of stress con~ons on the acute toxicity of this pesticide. The present paper reports data on the effects of pre-treatment of rats with phenobarbital, 3,4 benzpyrene, DDT and SKF-525A on the LD50 of parathion in rats, in vitro plasma esterase, liver carboxylesterase and p~athl-~degradation.