2024-03-28T17:45:39Z
https://soar-ir.repo.nii.ac.jp/oai
oai:soar-ir.repo.nii.ac.jp:00003935
2022-12-14T04:40:30Z
461:462
Polyenephosphatidylcholine prevents alcoholic liver disease in PPARα-null mice through attenuation of increases in oxidative stress
Okiyama, W
Tanaka, N
Nakajima, T
Tanaka, E
Kiyosawa, K
Gonzalez, FJ
Aoyama, T
Background/Aims: Alcoholic liver disease (ALD) is one of the leading causes of cirrhosis and yet efficient therapeutic strategies are lacking. Polyenephosphatidylcholine (PPC), a major component of essential phospholipids, prevented alcoholic liver fibrosis in baboons, but its precise mechanism remains uncertain. We aimed to explore the effects of PPC on ALD using ethanol-fed peroxisome proliferator-activated receptor α (Ppara)-null mice, showing several similarities to human ALD. Methods: Male wild-type and Ppara-null mice were pair-fed a Lieber-DeCarli control or 4% ethanol-containing diet with or without PPC (30 mg/kg/day) for 6 months. Results: PPC significantly ameliorated ethanol-induced hepatocyte damage and hepatitis in Ppara-null mice. These effects were likely a consequence of decreased oxidative stress through down-regulation of reactive oxygen species (ROS)-generating enzymes, including cytochrome P450 2E1, acyl-CoA oxidase, and NADPH oxidases, in addition to restoration of increases in Toll-like receptor 4 and CD14. PPC also decreased Bax and truncated Bid, thus inhibiting apoptosis. Furthermore, PPC suppressed increases in transforming growth factor-β1 expression and hepatic stellate cell activation, which retarded hepatic fibrogenesis. Conclusions: PPC exhibited anti-inflammatory, anti-apoptotic, and anti-fibrotic effects on ALD as a result of inhibition of the overexpression of ROS-generating enzymes. Our results demonstrate detailed molecular mechanisms of the anti-oxidant action of PPC.
Article
Journal of Hepatology 50(6): 1236-1246(2009)
Elsevier Science B.V.
2009-06
eng
journal article
AM
http://hdl.handle.net/10091/3107
https://soar-ir.repo.nii.ac.jp/records/3935
http://www.elsevier.com/wps/find/journaldescription.cws_home/621507/description
http://www.elsevier.com/wps/find/journaldescription.cws_home/621507/description
https://pubmed.ncbi.nlm.nih.gov/19398233
19398233
https://doi.org/10.1016/j.jhep.2009.01.025
10.1016/j.jhep.2009.01.025
0168-8278
AA10459105
Journal of Hepatology
50
6
1236
1246
https://soar-ir.repo.nii.ac.jp/record/3935/files/JHE-2008-1619-R1.pdf
application/pdf
146.4 kB
2015-09-24