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

Background: Rheumatoid arthritis (RA) is a progressive, chronic inflammatorydisease with uncertain pathogenesis. It is characterized by polyarthritis and highconcentrations of pro-inflammatory cytokines. There is a growing body of evidenceindicates that free radicals play an important role in the pathophysiology of thechronic inflammatory state associated with rheumatoid arthritis. Alpha-lipoic acid(α-LA) is a naturally occurring dithiol compound which is known to elicit a unique setof biochemical activities with potential potent biological antioxidant effect. Also, itmay 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 collageninducedarthritis. Also, the study discussed the possible mechanisms by which α-LAcan alleviate the severity of rheumatoid arthritis. Methods: The study was carried on30 of female rats divided into 3 groups: control group (group I), Collagen II-inducedarthritis group (group II) and CII + alpha lipoic acid treated group (group III).Rheumatoid arthritis was induced in rats of group II by immunizationwith100μg/100μl of emulsion of bovine collagen II in the base of the tail. Rats ofgroup 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 bodyweight was done in all groups throughout the experiment to assess the developmentand severity of arthritis. Biochemical analysis of blood samples of all groups hasbeen done to evaluate some markers of oxidative stress and inflammation markers.So, plasma levels of lipid peroxides (LPO), nitric oxide (NO) and superoxidedismutase (SOD) were measured for the evaluation of oxidative stress. Also, plasmalevels of prostaglandin E2 (PGE2), C-reactive protein (CRP) and tumor necrosisfactor-  (TNF-  ) were measured for evaluation of inflammation. Results:By end of the study, injection of rats of group II with collagen II induced arthriticmanifestations in all rats of this group with gradually progressive decrease of meanbody weight continued till end of the experiment. Treatment of rats of group III withα-LA led to improvement of most of the clinical arthritic parameters with significantattenuation in body weight loss in this group as compared to rats of group II. There isa significant increase in plasma level of oxidative stress markers in all rats of groupII 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 significantincrease in plasma level of inflammatory markers e.g., prostaglandin and C-reactiveprotein (PGE2 and CRP) as well as increase in plasma level of the pro-inflammatorycytokine; 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 significantincrease in plasma level of SOD as compared with group II. Additionally, there is asignificant 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 couldbe concluded that α-LA has a role to prevent oxidative stress and to supportantioxidant system against oxidative damage in collagen-induced arthritis model rats.Also, amelioration of joint damage in CIA rats by α-LA was associated with inhibitionof inflammatory process as indicated by lowering plasma level of TNF-α,prostaglandin and C-reactive protein. Results of the present study indicate that α-LAmay be a new adjunctive therapy for rheumatoid arthritis as it has a potentantioxidant as well as anti-inflammatory effect. Collectively, these findings mayencourage further exploration of the usefulness of lipoic acid in arthritis.