RESUMO
OBJECTIVE: To investigate the effect of metallothionein (MT) on rifampicin (RFP)-induced hepatotoxicity and the possible mechanisms. METHODS: Male MT- I / II null (MT-/-) and wild type (MT+/+) mice were randomly divided into 4 groups, respectively, and were orally administered RFP (50, 100 or 200 mg/kg) or equal volumes of solvent daily for 15 consecutive days. Levels of plasma alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DB) were determined. Liver indexes were calculated and liver histopathologic changes were examined by hematoxylin and eosin (HE) staining. The content of glutathione (GSH) as well as the activities of glutathione peroxydase (GPx) and glutathione reductases (GR) were measured in the liver homogenates. RESULTS: RFP treatment induced significant increases in plasma ALT, AST and DB, as well as liver index. Significant histopathologic changes which were charactered as fatty degeneration in liver were noteced. Moreover, augmentations of GSH content and GR activity and attenuation of GPx activity were observed. More severe hepatic injuries in MT-/- mice were observed as compared to MT+/+ mice, which were evidenced by higher liver/body weight ratio and GR activity, lower GSH content and GPx activity, and more serious fatty degeneration. CONCLUSION: RFP-induced hepatotoxicity was associated with cholestasis and oxidative damage. MT -/- mice were more susceptible than MT +/+ mice to RFP-induced hepatotoxicity and the enhanced hepatotoxicity involves increased oxidative stress.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Metalotioneína/farmacologia , Rifampina/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Técnicas de Inativação de Genes , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Rifampina/antagonistas & inibidoresRESUMO
Eleven BALB/c mouse strains of Beijing, Shanghai, Shenyang, Haerbin, Guangzhou, Chongqing and Changchun were monitored in order to assure the genetic quality of inbred BALB/c mouse strains in China and to estimate the credibility of microsatllite markers. Fourteen microsatellites loci on different chromosomes were investigated by PCR analysis. It showed that all these microsatellites DNA loci displayed single allelic gene band in mouse strains of Beijing, Shanghai and Haerbin. But the mice came from Shenyang, Guangzhou, Chongqing and Changchun had polymorphisms or heterozygosis, among which the Shenyang and Changchun strains showed polymorphisms and heterozygosis at two separate loci. Four loci showed polymorphisms or heterozygosis in one of the Guangzhou mouse strains. The Chongqing strains showed polymorphisms and heterozygosis at seven loci, including the D10Mit180 locus as compared with the Shanghai strains.