RESUMEN
Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.
Asunto(s)
Animales , Femenino , Antipirina/análogos & derivados , Apoptosis/efectos de los fármacos , Citocinas/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Depuradores de Radicales Libres/farmacología , Alanina Transaminasa/sangre , Antipirina/farmacología , Aspartato Aminotransferasas/sangre , /análisis , /metabolismo , /análisis , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Ensayo de Inmunoadsorción Enzimática , Endotoxinas/toxicidad , Galactosamina/toxicidad , Hepatocitos/efectos de los fármacos , Etiquetado Corte-Fin in Situ , /análisis , Lipopolisacáridos/toxicidad , Ratones Endogámicos BALB C , Distribución Aleatoria , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Leprosy patients treated formerly with dapsone monotherapy followed by combined therapy with rifampicin plus dapsone were surveyed for relapse and rifampicin resistance. The relapse rate was significantly low for the 482 multibacillary (MB) patients receiving > 12 months combined therapy compared with the 49 MB cases receiving < 12 months of combined therapy. The relapse rate was related to the duration of dapsone monotherapy prior to combined therapy. The difference in relapse rate in 247 paucibacillary (PB) patients following > 12 months combined therapy was also of significance, compared with the 66 PB cases who had received < 12 months combined therapy. Five strains of M. leprae isolated from relapsed patients were sensitive to rifampicin by mouse foot-pad test and all relapsed patients responded favourably to fixed duration MDT regimen for MB cases.