The correlation between the recovery rate of neurotoxic esterase activity and sensitivity to organophosphorus-induced delayed neurotoxicity.
Neurotoxic esterase (NTE) has been proposed to be the initiation site of organophosphorus compound-induced delayed neurotoxicity (OPIDN). There are two apparent problems associated with this hypothesis: NTE activity in the brain returns to nearly normal levels before the onset of the neuropathy, and NTE is present in and inhibited by organophosphorus compounds in young animals and other species which are relatively insensitive to the neurotoxic effects of these compounds. This paper presents data suggesting that differences in the recovery rates of NTE activity may account for some of these discrepancies. First, the onset of recovery of NTE activity following sc administration of 1.7 mg/kg of O,O-diisopropylphosphorofluoridate (DFP) in the hen sciatic nerve occurred several days later than in the brain. Furthermore, recovery was slower in distal than proximal parts of the nerve. This information indicates that NTE activity is depressed for a longer period at the site of the neuropathy than it would appear from the measurement of NTE activity in brain. Second, the rate of recovery of NTE activity was faster in the brains of chicks, of rats, and of hens treated with a daily po dose of 15 mg/kg cortisone acetate than it was in untreated hens. However, there was no significant increase in the NTE recovery rate in the peripheral nerves of the chicks or the cortisone-treated hens. Thus, it appears that although slower distal recovery could account for the greater sensitivity of longer axons to OPIDN, other factors are operating in chicks and cortisone-treated hens.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002645:Chickens; D003975:Diazepam / Q000494:pharmacology; D005260:Female; D007531:Isoflurophate / Q000633:toxicity*; D008297:Male; D010261:Paraoxon / Q000633:toxicity; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D011826:Radial Nerve / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects* / Q000201:enzymology
D007531:Isoflurophate; D010664:Phenylmethylsulfonyl Fluoride; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D003975:Diazepam; D010261:Paraoxon