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Titolo:
Protection from drug-induced hepatocellular changes by pretreatment with conjugating enzyme inhibitors in rats
Autore:
Sato, G; Aoki, T; Hosokawa, S; Sagami, F; Tsukidate, K;
Indirizzi:
Eisai & Co Ltd, Exploratory Safety Assessment Res, Tsukuba, Ibaraki 3002635, Japan Eisai & Co Ltd Tsukuba Ibaraki Japan 3002635 kuba, Ibaraki 3002635, Japan Eisai & Co Ltd, Dept Dev Safety Assessment Res, Gifu 5016195, Japan Eisai & Co Ltd Gifu Japan 5016195 ty Assessment Res, Gifu 5016195, Japan
Titolo Testata:
LIFE SCIENCES
fascicolo: 24, volume: 68, anno: 2001,
pagine: 2665 - 2673
SICI:
0024-3205(20010504)68:24<2665:PFDHCB>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
METABOLIC-ACTIVATION; SULFATION; LIVER; 2,6-DICHLORO-4-NITROPHENOL; PENTACHLOROPHENOL; INVIVO;
Keywords:
E2011; MAO inhibitor; rat; liver; acetyltransferase; pentachlorophenol;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Sato, G Eisai & Co Ltd, Exploratory Safety Assessment Res, 5-1-3 Tokodai, Tsukuba,Ibaraki 3002635, Japan Eisai & Co Ltd 5-1-3 Tokodai Tsukuba IbarakiJapan 3002635 , Japan
Citazione:
G. Sato et al., "Protection from drug-induced hepatocellular changes by pretreatment with conjugating enzyme inhibitors in rats", LIFE SCI, 68(24), 2001, pp. 2665-2673

Abstract

The present paper describes the role of conjugating enzymes in the development of hepatotoxicity after administration of repeated doses of a novel monoamine oxidase type-A (MAO-A) inhibitor, (5R)3-[2-(1S)-3-cyano-1 -hydroxypropyl)benzothiazol-6-yl]-5-methoxymethyl-2-oxazolidinine (E2011). The effects of pretreatment with three kinds of conjugating enzyme inhibitors on hepatic lesions induced by E2011 were evaluated in female Sprague-Dawley rats. The inhibitors used were 2,6-dichloro-4-nitrophenol (DCNP; inhibitor of sulfotransferase (ST)), pentachlorophenol (PCP; inhibitor of both ST and acetyltransferase (AT) or ranitidine (inhibitor of UDP-glucuronosyltransferase (UDP-GT)). Two weeks treatment of E2011 alone at an oral dosage of 150 mg/kg induced hepatocellular changes characterized by nuclear enlargement. Daily pretreatment with DCNP (10 mg/kg, i.p.) enhanced the E2011-induced hepatocellular changes accompanied by single cell necrosis. On the other hand, the hepatotoxicity was clearly diminished by PCP (5 mg/kg, i.p.). Ranitidine pretreatment had no effect. Protection by PCP was attributed to the inhibitory effects of AT in addition to ST; it was considered that the hepatocellular changes caused by E2011 were largely dependent on the formation of acetyl conjugate(s), (C) 2001 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 08:38:28