RESUMEN
D-Galactosamine (GalN) induces acute hepatitis in experimental animals; this hepatitis has been shown to be suppressed by oral or intraperitoneal administration of modified arabinoxylan from rice bran (MGN-3), and active low molecular fraction isolated from MGN-3 (LMW). We previously reported that this protective mechanism is mediated in part by downregulation of interleukin-18 (IL-18). The present study shows for the first time that nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) and CD14 are involved in the suppressive action of LMW on GalN-induced hepatitis. Wistar rats (aged 4 weeks, SLC) were intraperitoneally treated with either MGN-3 or LMW. Then, rats were given GalN at 400mg/kg at 1h after the initial treatment. The serum activity of transaminases (ALT and AST) was significantly higher after GalN treatment; these changes were attenuated by MGN-3 and LMW. Furthermore, LMW abrogated inhibitor of κB kinase (IκB) degradation induced by GalN, and this was associated with the inhibition of NF-κB activation. Moreover, phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase (JNK) protein expression in the liver after GalN treatment was significantly higher, and LMW reduced this increase. We also found that GalN treatment induced TLR4 and CD14 mRNA expression, and LMW significantly inhibited CD14 mRNA expression. These results suggest that the suppressive effects of LMW on GalN-induced hepatitis are possibly related to inhibition of NF-κB, JNK phosphorylation and CD14 expression.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , FN-kappa B/antagonistas & inhibidores , Oryza/química , Xilanos/farmacología , Animales , Caspasa 1/genética , Caspasa 1/metabolismo , Galactosamina/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Receptores de Lipopolisacáridos/genética , Receptores de Lipopolisacáridos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , FN-kappa B/genética , FN-kappa B/metabolismo , Ratas , Ratas Wistar , Transducción de Señal , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Xilanos/químicaRESUMEN
We investigated in this study the effect of modified arabinoxylan from rice bran (MGN-3) and its fractions on D-galactosamine (D-GalN)-induced IL-18 expression and hepatitis in rats. Male Wistar rats were pretreated with MGN-3 or fractions of the MGN-3 hydrolysate, or with saline 1 h before administering D-GalN (400 mg/kg B.W.). The serum transaminase activities, IL-18 mRNA expression level in the liver and IL-18 concentration in the serum were determined 24 h after injecting D-GalN. Both the oral and intraperitoneal administration of MGN-3 (20 mg/kg B.W.) alleviated D-GalN-induced hepatic injury under these experimental conditions. The low-molecular-weight fraction (LMW) of MGN-3 showed the strongest protective effect on D-GalN-induced liver injury, its main sugar component being glucose. Moreover, the D-GalN-induced IL-18 expression was significantly reduced by treating with MGN-3 and LMW. The results suggest that MGN-3 and LMW could provide significant protection against D-GalN liver injury, and that IL-18 might be involved in their protective influence.