α-Lipoic acid inhibits liver fibrosis through the attenuation of ROS-triggered signaling in hepatic stellate cells activated by PDGF and TGF-β.
Reactive oxygen species (ROS) have been implicated in hepatic stellate cell activation and liver fibrosis. We previously reported that α-lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA) inhibited toxicant-induced inflammation and ROS generation. In the present study, we further examined the effects of LA/DHLA on thioacetamide (TAA)-induced liver fibrosis in rats and the possible underlying mechanisms in hepatic stellate cells in vitro. We found that co-administration of LA to rats chronically treated with TAA inhibited the development of liver cirrhosis, as indicated by reductions in cirrhosis incidence, hepatic fibrosis, and AST/ALT activities. We also found that DHLA inhibited TGF-β/PDGF-stimulated HSC-T6 activation and ROS generation. These effects could be mediated by the MAPK and PI3K/Akt pathways. According to our current results, LA may have a beneficial role in the treatment of chronic liver diseases caused by ongoing hepatic damage.
Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan.
Ning-Ping
NP
Foo
Shu-Huei
SH
Lin
Yu-Hsuan
YH
Lee
Ming-Jiuan
MJ
Wu
Ying-Jan
YJ
Wang
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D000077214:Becaplermin; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000633:toxicity; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011994:Recombinant Proteins / Q000633:toxicity; D008063:Thioctic Acid / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000633:toxicity
D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000077214:Becaplermin; D008063:Thioctic Acid; C015144:dihydrolipoic acid