RRC ID |
63623
|
著者 |
Li SW, Takahara T, Que W, Fujino M, Guo WZ, Hirano SI, Ye LP, Li XK.
|
タイトル |
Hydrogen-rich water protects against liver injury in nonalcoholic steatohepatitis through HO-1 enhancement via IL-10 and Sirt 1 signaling.
|
ジャーナル |
Am J Physiol Gastrointest Liver Physiol
|
Abstract |
Nonalcoholic steatohepatitis (NASH) could progress to hepatic fibrosis when absence of effective control. The purpose of our experiment was to investigate the protective effect of drinking water with high concentration of hydrogen in our study named hydrogen rich water (HRW) on mice with non-alcoholic fatty liver disease to elucidate the mechanism underlying the molecular hydrogen therapeutic action. The choline-supplemented, L-amino acid-defined (CSAA) or choline-deficient, L-amino acid-defined (CDAA) diet for 20 weeks were used to induce NASH and fibrosis in the mice model and simultaneously treated with HRW for different periods of time. Primary hepatocytes were stimulated by palmitate in order to mimic a liver lipid metabolism during fatty liver formation. Mice in the CSAA + HRW group had lower serum levels of ALT and AST and milder histological damage. The inflammatory cytokines were expressed at lower levels in the HRW group than in the CSAA group. Importantly, HRW reversed hepatocyte apoptosis as well as hepatic inflammation and fibrosis in pre-existing hepatic fibrosis specimens. Molecular hydrogen inhibits the lipopolysaccharide-induced production of inflammation cytokines through an HO-1/IL-10-independent pathway. Furthermore, HRW improved hepatic steatosis in the CSAA + HRW group. Sirt1 induction by molecular hydrogen via the HO-1/AMPK/PPARα/PPARγ pathway suppresses palmitate-mediated abnormal fat metabolism. Orally administered HRW suppressed steatosis induced by CSAA and attenuated fibrosis induced by CDAA, possibly by reducing oxidative stress and the inflammation response.
|
巻・号 |
320(4)
|
ページ |
G450-G463
|
公開日 |
2021-4-1
|
DOI |
10.1152/ajpgi.00158.2020
|
PMID |
33439102
|
MeSH |
Animals
Heme Oxygenase-1 / metabolism*
Hepatocytes / drug effects*
Hepatocytes / enzymology
Hepatocytes / pathology
Hydrogen / chemistry
Hydrogen / pharmacology*
Interleukin-10 / metabolism*
Kupffer Cells / drug effects
Kupffer Cells / metabolism
Lipolysis / drug effects
Liver / drug effects*
Liver / enzymology
Liver / pathology
Liver Cirrhosis, Experimental / enzymology
Liver Cirrhosis, Experimental / pathology
Liver Cirrhosis, Experimental / prevention & control*
Male
Membrane Proteins / metabolism*
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease / enzymology
Non-alcoholic Fatty Liver Disease / pathology
Non-alcoholic Fatty Liver Disease / prevention & control*
RAW 264.7 Cells
Signal Transduction
Sirtuin 1 / metabolism*
Water / pharmacology*
|
IF |
3.725
|
リソース情報 |
ヒト・動物細胞 |
RAW 264(RCB0535) |