THE PROTECTIVE EFFECT OF ALDRIN AGAINST THE TOXICITY OF ORGANOPHOSPHATE ANTICHOLINESTERASES

¹ Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania

A single oral dose of 16 mg/kg of aldrin protected mice 4 days later against parathion, paraoxon, tetraethyl pyrophosphate, diisopropyl fluorophosphate, O-ethyl O-p-nitrophenylphosphorothiote, Guthion, tri-o-tolylphosphate and physostigmine, but not against octamethyl pyrophosphoramide (OMPA) or neostigmine. One hour after aldrin, the toxicity of parathion was increased, whereas, from 16 hr to 12 days after aldrin, animals were significantly protected. This effect of aldrin reached its maximum in about 4 days, and 1 mg/kg provided significant protection. Two days after aldrin, A-esterase, which detoxifies paraoxon, increased 38% in the liver but decreased 50% in the plasma, and plasma B-esterase, which is inhibited by paraoxon, was increased 24%. Aldrin had no effect on the inhibitory action of paraoxon on plasma cholinesterase, but it reduced this action of paraoxon in the brain. This is in accord with the finding that aldrin failed to protect against OMPA or neostigmine, which differ from the other anticholinesterases tested in being poor in vivo inhibitors of brain cholinesterase. Ethionine abolished the protective effect of aldrin against the toxicity and brain cholinesterase-inhibiting action of paraoxon and prevented the aldrin-induced increases in plasma B-esterase and liver A-esterase. Ethionine, alone, however, increased the mortalities after parathion and paraoxon. Though the increases in A- and B-esterases would be expected to decrease the toxicities of parathion and paraoxon, other factors possibly involving the central nervous system may play a role in aldrin's protective effect against organophosphate poisoning.

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