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Titolo:
RELATIVE POTENCIES OF THE 4 STEREOISOMERS OF ISOMALATHION FOR INHIBITION OF HEN BRAIN ACETYLCHOLINESTERASE AND NEUROTOXIC ESTERASE IN-VITRO
Autore:
JIANMONGKOL S; BERKMAN CE; THOMPSON CM; RICHARDSON RJ;
Indirizzi:
UNIV MICHIGAN,NEUROTOXICOL RES LABS,TOXICOL PROGRAM,109 OBSERV ANN ARBOR MI 48109 UNIV MICHIGAN,SCH PUBL HLTH,DEPT ENVIRONM & IND HLTH,TOXICOL PROGRAM ANN ARBOR MI 48109 UNIV MICHIGAN,SCH MED,DEPT NEUROL ANN ARBOR MI 48109 UNIV MICHIGAN,NEUROSCI PROGRAM ANN ARBOR MI 48109 SEATTLE BIOMED RES INST SEATTLE WA 98119 UNIV MONTANA,DEPT CHEM MISSOULA MT 59812
Titolo Testata:
Toxicology and applied pharmacology
fascicolo: 2, volume: 139, anno: 1996,
pagine: 342 - 348
SICI:
0041-008X(1996)139:2<342:RPOT4S>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROPATHY TARGET ESTERASE; INDUCED DELAYED NEUROTOXICITY; ORGANOPHOSPHATE POLYNEUROPATHY; PHENYLMETHANESULFONYL FLUORIDE; MALATHION; POTENTIATION; ENANTIOMERS; KINETICS; MALAOXON; INVITRO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
S. Jianmongkol et al., "RELATIVE POTENCIES OF THE 4 STEREOISOMERS OF ISOMALATHION FOR INHIBITION OF HEN BRAIN ACETYLCHOLINESTERASE AND NEUROTOXIC ESTERASE IN-VITRO", Toxicology and applied pharmacology, 139(2), 1996, pp. 342-348

Abstract

The cholinergic toxicity of malathion is exacerbated by its isomerization product, isomalathion, which inhibits detoxifying carboxylesterases as well as target acetylcholinesterase (AChE). Previous work has shown that the four stereoisomers of isomalathion, (1R, 3R), (1R, 3S), (1S, 3R), and (1S, 3S), differ in their inhibitory potencies against either rat brain or electric eel AChE. The present study examined the relative inhibitory potencies of these stereoisomers and the totally racemic mixture (1RS, 3RS) against hen brain AChE and neurotoxic esterase(NTE) to provide new data on stereoselective inhibition of neurotoxicologically significant esterases and to assess the potential of these compounds to cause organophosphorus (OP) compound-induced delayed neurotoxicity (OPIDN). The order of potencies against hen brain AChE was (1R, 3R) > (1R, 3S)>(1RS, 3RS)>(1S, 3R)> (1S, 3S), with a 15-fold difference between the strongest (k(i) = 388 mM(-1) min(-1); 20 min I50 = 89.3 nM) and weakest (k(i) = 25.6 mM(-1) min(-1); 20 min I50 = 1354 nM)inhibitors. Both asymmetric centers contributed substantially and interdependently to inhibitory potency, but the effect of changing the configuration at phosphorus alone was greater than changing the configuration at carbon alone. None of the isomalathions was an effective inhibitor of hen brain NTE (extrapolated 20 min I50 values were 1.2 to 29 mM, yielding NTE/AChE I50 ratios (neuropathy target ratios, NTRs) of 1.5 x 10(3) to 1.5 x 10(5). NTRs of this magnitude indicate that none of the isomalathions should initiate OPIDN, even after doses greatly exceeding the LD50. Therefore, reports of OPIDN or other neuropathic sequelae associated with malathion exposures in humans cannot be explained on the basis of NTE inhibition by contaminating isomalathions. (C) 1996 Academic Press, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 17:54:58