Antioxidant and Anti-inflammatory Effects of Alpha- Lipoic Acid in Collagen II-induced Arthritis in Rats | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Article 1, Volume 30, Issue 2, June 2010, Page 1-20 PDF (313.86 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2010.36294 | ||||
 View on SCiNiTO | ||||
| Author | ||||
| Mona El-Karn* | ||||
| Department of Medical Physiology, Faculty of Medicine, Assiut University | ||||
| Abstract | ||||
| 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. | ||||
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