Galactose protects hepatocytes against TNF-α-induced apoptosis by promoting activation of the NF-κB signaling pathway in acute liver failure.
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.
Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Yanmin
Y
Liu
1] Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China [2] Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
Liuluan
L
Zhu
1] Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China [2] Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
Shuntao
S
Liang
Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Shanshan
S
Yao
1] Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China [2] Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
Rui
R
Li
1] Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China [2] Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China [3] School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China.
Sanhai
S
Liu
Institute of Basic Medical Theory of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
Yaluan
Y
Ma
Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Xiaobing
X
Zhou
Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Jinliang
J
Zhang
1] Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China [2] Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
Hui
H
Zeng
Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Xianbo
X
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D005690:Galactose / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D017114:Liver Failure, Acute / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016207:Cytokines; D016328:NF-kappa B; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D005690:Galactose