Insights in the mechanism underlying the protective effect of α-lipoic acid against acetaminophen-hepatotoxicity.
Eur J Pharmacol
; 726: 116-23, 2014 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-24486394
ABSTRACT
Acetaminophen (APAP) is one of the most widely used analgesic antipyretic drugs and is a major cause of acute liver failure at overdose. The aim of this study is to investigate the possible protective effect of α-lipoic acid (α-LA, 20 or 100 mg/kg administered simultaneously or after 1.5 h) against APAP-induced hepatotoxicity in rats. Administration of APAP (1.5 g/kg i.p.) resulted in elevation of serum ALT and hepatic malondialdehyde (MDA) content, as well as decrease in hepatic glutathione (GSH) content. In addition, elevation in hepatic hemeoxygenase-1 (HO-1) and NADPH oxidase expression was observed accompanied with a significant reduction in glutathione synthase and cystathionine-beta-synthase (CßS) expression. Furthermore, nuclear factor kappa-B (NF-κB) activity was enhanced in APAP-treated rats. Administration of the standard APAP antidote; N-acetylcysteine (NAC, 1200 mg/kg) or α-LA (20 mg/kg), simultaneously or 1.5 h after APAP, ameliorated APAP-induced alterations in liver function, oxidant and inflammatory markers. Importantly, simultaneous administration of NAC or α-LA (20 mg/kg) was more protective than their later administration. However, the beneficial effect of α-LA was lost at higher dose level (100 mg/kg). Taken together, the beneficial effects of α-lipoic acid (20 mg/kg) were comparable to those of NAC which provides a new possible treatment for APAP-induced hepatotoxicity in patients who cannot tolerate NAC. However, careful dose selection is warranted since the beneficial effects of α-LA were lost at higher doses.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Tióctico
/
Citoproteção
/
Doença Hepática Induzida por Substâncias e Drogas
/
Fígado
/
Acetaminofen
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2014
Tipo de documento:
Article