Antioxidant and Anti-inflammatory Effects of Alpha- Lipoic Acid in Collagen II-induced Arthritis in Rats

Background: Rheumatoid arthritis (RA) is a progressive, chronic inflammatory
disease with uncertain pathogenesis. It is characterized by polyarthritis and high
concentrations of pro-inflammatory cytokines. There is a growing body of evidence
indicates that free radicals play an important role in the pathophysiology of the
chronic inflammatory state associated with rheumatoid arthritis. Alpha-lipoic acid
(α-LA) is a naturally occurring dithiol compound which is known to elicit a unique set
of biochemical activities with potential potent biological antioxidant effect. Also, it
may play a role in modulation of various inflammatory signaling pathways.
Objective: The purpose of this study was to assess the efficacy of alpha-lipoic acid (α-
LA), to attenuate the development of rheumatoid arthritis in rat model of collageninduced
arthritis. Also, the study discussed the possible mechanisms by which α-LA
can alleviate the severity of rheumatoid arthritis. Methods: The study was carried on
30 of female rats divided into 3 groups: control group (group I), Collagen II-induced
arthritis group (group II) and CII + alpha lipoic acid treated group (group III).
Rheumatoid arthritis was induced in rats of group II by immunization
with100μg/100μl of emulsion of bovine collagen II in the base of the tail. Rats of
group III were injected by CII, and received α-LA daily (100 mg/kg/day/
intraperitonially) for 42 day. Clinical evaluation of arthritis and follow up of body
weight was done in all groups throughout the experiment to assess the development
and severity of arthritis. Biochemical analysis of blood samples of all groups has
been done to evaluate some markers of oxidative stress and inflammation markers.
So, plasma levels of lipid peroxides (LPO), nitric oxide (NO) and superoxide
dismutase (SOD) were measured for the evaluation of oxidative stress. Also, plasma
levels of prostaglandin E2 (PGE2), C-reactive protein (CRP) and tumor necrosis
factor- (TNF-) were measured for evaluation of inflammation. Results:
By end of the study, injection of rats of group II with collagen II induced arthritic
manifestations in all rats of this group with gradually progressive decrease of mean
body weight continued till end of the experiment. Treatment of rats of group III with
α-LA led to improvement of most of the clinical arthritic parameters with significant
attenuation in body weight loss in this group as compared to rats of group II. There is
a significant increase in plasma level of oxidative stress markers in all rats of group
II as indicated by increased serum level of lipid peroxides (LPO) and nitric oxide
(NO), with a significant reduction in plasma level of superoxide dismutase (SOD)
when compared with levels of control group. Also, the study revealed a significant
increase in plasma level of inflammatory markers e.g., prostaglandin and C-reactive
protein (PGE2 and CRP) as well as increase in plasma level of the pro-inflammatory
cytokine; TNF-α in CIA rats (group II). Administration of α-LA to rats of group III 
induced significant reduction of plasma level of LPO and NO with significant
increase in plasma level of SOD as compared with group II. Additionally, there is a
significant reduction in plasma levels of the measured inflammatory markers ((PGE2,
CRP and TNF-α) in rats of group III as compared with group II. Conclusion: It could
be concluded that α-LA has a role to prevent oxidative stress and to support
antioxidant system against oxidative damage in collagen-induced arthritis model rats.
Also, amelioration of joint damage in CIA rats by α-LA was associated with inhibition
of inflammatory process as indicated by lowering plasma level of TNF-α,
prostaglandin and C-reactive protein. Results of the present study indicate that α-LA
may be a new adjunctive therapy for rheumatoid arthritis as it has a potent
antioxidant as well as anti-inflammatory effect. Collectively, these findings may
encourage further exploration of the usefulness of lipoic acid in arthritis.