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Titolo:
Paracetamol (acetaminophen)-induced toxicity: Molecular and biochemical mechanisms, analogues and protective approaches
Autore:
Bessems, JGM; Vermeulen, NPE;
Indirizzi:
Vrije Univ Amsterdam, Leiden Amsterdan Ctr Dug Res, Div Mol Toxicol, Dept Pharmacochem, NL-1081 HV Amsterdam, Netherlands Vrije Univ Amsterdam Amsterdam Netherlands NL-1081 HV erdam, Netherlands
Titolo Testata:
CRITICAL REVIEWS IN TOXICOLOGY
fascicolo: 1, volume: 31, anno: 2001,
pagine: 55 - 138
SICI:
1040-8444(2001)31:1<55:P(TMAB>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACETAMINOPHEN-INDUCED HEPATOTOXICITY; PARA-BENZOQUINONE IMINE; ISOLATED RAT HEPATOCYTES; INDUCED HEPATIC NECROSIS; PROSTAGLANDIN-H SYNTHASE; REACTIVE METABOLITE FORMATION; ISOLATED MOUSE HEPATOCYTES; HUMAN-LIVER-MICROSOMES; ACUTE-RENAL-FAILURE; PERFORMANCE LIQUID-CHROMATOGRAPHY;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
423
Recensione:
Indirizzi per estratti:
Indirizzo: Vermeulen, NPE Vrije Univ Amsterdam, Leiden Amsterdan Ctr Dug Res, Div MolToxicol, Dept Pharmacochem, De Boelelaan 1083, NL-1081 HV Amsterdam, Netherlands Vrije Univ Amsterdam De Boelelaan 1083 Amsterdam Netherlands NL-1081 HV
Citazione:
J.G.M. Bessems e N.P.E. Vermeulen, "Paracetamol (acetaminophen)-induced toxicity: Molecular and biochemical mechanisms, analogues and protective approaches", CR R TOXIC, 31(1), 2001, pp. 55-138

Abstract

An overview is presented on the molecular aspects of toxicity due to paracetamol (acetaminophen) and structural analogues. The emphasis is on four main topics, that is, bioactivation, detoxication, chemoprevention, and chemoprotection. In addition, some pharmacological and clinical aspects are discussed briefly. A general introduction is presented on the biokinetics, biotransformation, and structural modification of paracetamol. Phase II biotransformation in relation to marked species differences and interorgan transport of metabolites are described in detail, as are bioactivation by cytochrome P450 and peroxidases, two important phase I enzyme families. Hepatotoxicity is described in depth, as it is the most frequent clinical observation after paracetamol-intoxication. In this context, covalent protein binding and oxidative stress are two important initial (Stage I) events highlighted. In addition, the more recently reported nuclear effects are discussed as well as secondary events (Stage II) that spread over the whole liver and maybe relevant targets for clinical treatment. The second most frequent clinical observation, renal toxicity, is described with respect to the involvement of prostaglandin synthase, N-deacetylase, cytochrome P450 and glutathione S-transferase. Lastly, mechanism-based developments of chemoprotective agents and progress in the development of structural analogues with an improved therapeutic index are outlined.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 13:33:48