To study the effect and mechanism of dimethyl fumarate [DMF] in adjuvant induced arthritis model in rats

Shruti Saha,Jagjit Singh,Rohit Kumar,Neha Singh,Amitava Chakrabarti,Alka Bhatia,Lekha Saha

doi:10.22631/rr.2020.69997.1101

Shruti Saha, Jagjit Singh + Show 5 more

Open Access

https://doi.org/10.22631/rr.2020.69997.1101

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Abstract

Currently available disease modifying anti-rheumatoid drugs have limitations like dose-dependent toxicity and tolerance.Dimethyl fumarate has demonstrated anti-inflammatory and immunomodulatory properties in various animal models. Thus, thepresent study aimed to evaluate the effects and mechanism of DMF in a murine model of adjuvant-induced arthritis.A total of 84 rats were divided into early treatment groups (n=48) and late treatment groups (n=36). There were 8 subgroupsand 6 subgroups (n=6 in each group) in the early and late treatment groups, respectively. Experimental rheumatoid arthritis(RA) was induced in Wistar rats by injecting complete Freund's adjuvant (CFA) intradermally at the base of the tail. Antirheumatic effects were evaluated by arthritis and histopathological scoring of ankle joints. To evaluate anti-oxidant properties,GSH, catalase, SOD, and lipid peroxidation were measured. ESR, WBC count, TNF-α and IL-6 levels were measured to evaluatethe immunomodulatory properties of DMF. DMF demonstrated anti-inflammatory effects by decreasing arthritis andhistopathological scores compared to the CFA control group, though the difference was not statistically significant. DMFexhibited immunomodulatory properties as decreases in TLC count, serum TNF-α, and plasma IL-6 levels were observed. In allthe above-mentioned parameters, the best response was achieved with the early combination therapy of DMF 30 mg/kg andmethotrexate [Mtx] 0.1 mg/kg. In the present study, DMF demonstrated antirheumatoid effects in a rat model of CFA-inducedarthritis. The best antirheumatoid effect was achieved with the early combination of DMF and Mtx.

Highlights

Rheumatoid arthritis [rheumatoid arthritis (RA)] is a chronic inflammatory autoimmune connective tissue disease which characteristically causes the gradual ongoing destruction of articular cartilage and resorption of bone, leading to disability and premature mortality [1,2,3]
DMF alone demonstrated some anti-inflammatory effects by decreasing arthritis and histopathological scorings compared with the complete Freund's adjuvant (CFA) control group in both the early and late treatment groups, but those decreases was not statistically significant
In all the above-mentioned parameters, the best response was observed in the early combination therapy of DMF 30 mg/kg and Mtx 0.1 mg/kg, which was comparable with the response of the Mtx 0.25 mg/kg group

Summary

Introduction

Rheumatoid arthritis [RA] is a chronic inflammatory autoimmune connective tissue disease which characteristically causes the gradual ongoing destruction of articular cartilage and resorption of bone, leading to disability and premature mortality [1,2,3]. It is the most common form of polyarticular inflammatory arthritis [1], and multiple epidemiological studies determined the 2000– 2015 incidence rate to be 18.5 cases per 100,000 personyears; the prevalence was 0.329% by January 2015 [4]. Complete Freund’s adjuvant (CFA) is most commonly used, as the development of this RA model is easy and has been standardized over the years [6]

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