Surina Zheng, Shunsuke Sugita, Shizuka Hirai, Yukari Egashira
Laboratory of Food and Nutrition, Graduate School of Horticulture, Chiba University, 648 Matsudo, Matsudo-shi, Chiba 271-8510, Japan
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 400 mg/kg at 1 h 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.
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