In vitro modifications of rat NTE and other esterases by chemicals which induce delayed neurotoxicity in vivo.
A rat in vitro model has been developed which permits direct study of the biochemical mechanisms involved in delayed neurotoxicity induced by any chemical compound, not only organophosphates. Using rat brain homogenate, a parallel study on the activity of neurotoxic esterase (NTE) and total esterases (TE) compared the action of metamidophos, which is known to induce delayed neurotoxicity, and the synthetic fatty acid anilides, oleylanilide and linoleylanilide. Inhibition in the activity of NTE and TE, unrelated to the concentration and the incubation time assayed, was caused by metamidophos, while the anilides showed a 2-phase concentration-time dependent behaviour. This confirmed the results we previously obtained in vivo. In both cases the appearance of delayed neuropathy was related to modification of NTE activity. We concluded that phosphorylation of the enzyme may not be the only biochemical requirement for the development of delayed neurotoxicity syndromes in which modification of NTE is produced.
Blasco
R
R
Instuto Nacional de Toxicologia, Sevilla, Spain.
Moreno
E
E
Sanz
P
P
Repetto
M
M
D000813:Anilides / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004950:Esterases / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D009422:Nervous System Diseases / Q000139:chemically induced / Q000201:enzymology; D009943:Organophosphorus Compounds / Q000633:toxicity; D009946:Organothiophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000813:Anilides; D009943:Organophosphorus Compounds; D009946:Organothiophosphorus Compounds; C014655:methamidophos; D004950:Esterases; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase