Ketoconazole inhibits acetaminophen-induced hepatotoxicity in mice.
Eur J Gastroenterol Hepatol
; 7(8): 757-62, 1995 Aug.
Article
em En
| MEDLINE
| ID: mdl-7496865
ABSTRACT
OBJECTIVE:
To investigate the effect of ketoconazole on acetaminophen (AAP)-induced hepatotoxicity in mice. MATERIALS ANDMETHODS:
Mice were given AAP intragastrically (300 mg/kg) and treated with ketoconazole (100 mg/kg intraperitoneally) or saline either 30 min before or 2-3 h after AAP administration. Mortality was recorded for 48 h, during which all mice given saline either died or recovered fully. Serum alanine and aspartate transaminase levels were determined 24 h after administration of AAP. Prostaglandin E2, thromboxane A2 and leukotriene C4 production was determined 6 h after AAP administration in the supernatants from the short-term culture of liver fragments by radioimmunoassay.RESULTS:
Ketoconazole significantly decreased mortality and transaminase levels when given to mice either 30 min before or 2 h after AAP. Liver fragments from mice with AAP hepatitis produced greater quantities of prostaglandin E2, thromboxane A2 and leukotriene C4 than fragments from normal liver. Pretreatment of mice with ketoconazole or its addition to liver fragments ex vivo further increased the production of prostaglandin E2 and reduced the production of thromboxane A2. The effect of ketoconazole on leukotriene C4 synthesis was different in vivo (synthesis stimulation) from in vitro (synthesis inhibition).CONCLUSION:
The protective effect of ketoconazole in AAP hepatitis is most probably mediated by modulation of eicosanoid synthesis by liver cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_digestive_diseases
Assunto principal:
Doença Hepática Induzida por Substâncias e Drogas
/
Cetoconazol
/
Acetaminofen
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Gastroenterol Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Croácia