Alpha-lipoic acid suppresses the development of collagen-induced arthritis and protects against bone destruction in mice.
OBJECTIVE
To test the ability of alpha-lipoic acid (LA) to attenuate the development of collagen-induced arthritis (CIA) in mice.


METHODS
Mice were divided into three groups and treated with intraperitoneal administration of LA (10 or 100 mg/kg) or placebo. Clinical, histologic, and biochemical parameters were assessed. Human synovial fibroblasts and peripheral blood mononuclear cells were cocultured in various concentrations of LA to evaluate the effects on osteoclastogenesis.


RESULTS
LA was associated with a dose-dependent reduction of CIA, as well as preventing bone erosion and destructive changes. Intracellular reactive oxygen species in lymphocytes obtained from inguinal lymph nodes, which was significantly higher in CIA than control mice, was significantly reduced in CIA by LA. The concentrations of TNF-alpha, IL-1beta, and IL-6 in the paws, and synovial NF-kappaB binding, all of which were markedly higher in CIA than control mice, were reduced by treatment with LA. In addition, LA inhibited the formation of human osteoclasts in vitro.


CONCLUSIONS
Amelioration of joint disease by LA was associated with reduction in oxidative stress, as well as inhibition of inflammatory cytokine activation and NF-kappaB DNA binding activity. Moreover, LA inhibited bone destruction in vivo and osteoclastogenesis in vitro. Collectively, these results indicate that LA may be a new adjunctive therapy for rheumatoid arthritis.
Lee
Eun Young
EY
Division of Allergy and Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Republic of Korea.
Lee
Chang-Keun
CK
Lee
Ki-Up
KU
Park
Joong Yeol
JY
Cho
Kyung-Ja
KJ
Cho
You Sook
YS
Lee
Hee Ran
HR
Moon
Se Hwan
SH
Moon
Hee-Bom
HB
Yoo
Bin
B
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D016207:Cytokines; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D011897:Random Allocation; D013582:Synovial Fluid / Q000187:drug effects / Q000276:immunology; D008063:Thioctic Acid / Q000494:pharmacology*
D000975:Antioxidants; D016207:Cytokines; D016328:NF-kappa B; D008063:Thioctic Acid