Galactose protects hepatocytes against TNF-[alpha]-induced apoptosis by promoting activation of the NF-[kappa]B signaling pathway in acute liver failure

• Published in: Laboratory investigation 2015-05, Vol.95 (5), p.504
• Main Authors: Liu, Yanmin, Zhu, Liuluan, Liang, Shuntao, Yao, Shanshan, Li, Rui, Liu, Sanhai, Ma, Yaluan, Zhou, Xiaobing, Zhang, Jinliang, Zeng, Hui, Wang, Xianbo
• Format: Article
• Language: English
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.2015.34

Saccharides are reported to protect hepatocytes from acute liver injury through distinct mechanisms. To date, the protective role of galactose against acute liver injury induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN) has been attributed to competition with D-GalN. Here, we showed that in addition to its effects on LPS/D-GalN and tumor necrosis factor alpha (TNF-α)/D-GalN models, galactose improves hepatic injury in mice challenged with LPS alone or TNF-α/actinomycin D. Consistent with this result, galactose enhanced the viability of TNF-α-stimulated Chang Liver and Hu7.5 hepatic cell lines. Specifically, galactose prevented TNF-α-induced apoptosis of hepatocytes through promoting phosphorylation of nuclear factor kappa B (NF-κB) p65. Additionally, galactose enhanced expression of the anti-apoptotic genes, c-IAP1 and A20, and inhibited cleavage of caspase-8 and caspase-3. These findings collectively suggest that galactose prevents TNF-α-induced liver injury through activation of the NF-κB signaling pathway. Considering that monosaccharides protect against liver injury via distinct mechanisms, these compounds may represent a promising clinical approach to treat acute liver failure.