Anti – Rheumatic activity of 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide in CFA -induced Arthritis model

Abstract

Chronic inflammation is pathologically associated with various clinical conditions such as rheumatoid arthritis. Several anti-inflammatory and analgesic drugs currently available in market presents a wide range of problems. Therefore, current study was aimed to evaluate anti-inflammatory and analgesic activities of newly synthesized compound 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS). Carrageenan and CFA-induced models were developed for evaluation of anti-inflammatory and analgesic activity. Quantitative-Real-time PCR (qRT-PCR) was performed to determine the mRNA expression levels of inflammatory mediators. Pain behaviors were evaluated by performing Von Frey, Randall Selitto, cold acetone and hot plate test. X-rays imaging and hematoxyline and eosin staining was performed for examination of soft tissues of treated mice paw. Additionally, Kodzeila’s screen test and weight test was performed for determination of any side effect on motor function and muscle strength. Acute pre-treatment of animals with MOPBS (1, 10, 50 and 100 mg/kg, i.p.) produced a significant reduction of paw oedema against carrageenan-induced acute inflammation as well as notable inhibition of mechanical hyperalgesia, allodynia and thermal hyperalgesia. Similarly, in chronic inflammation model, administration of MOPBS (50 mg/kg, i.p.) produced a remarkable reduction of paw edema. Additionally, MOPBS pretreatment showed a significant inhibition of thermal hyperalgesia, mechanical allodynia, and mechanical hyperalgesia in chronic arthritis model. Several pro-inflammatory mediators such as Nitric oxide (NO), Vascular endothelial growth factor (VEGF), interleukins (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) were inhibited by MOPBS treatment in blood plasma and paw tissues respectively. MOPBS also enhanced the mRNA expression levels of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), superoxide dismutase (SOD2) and heme oxygenase (HO-1) and in turn reduced arthritis severity and inflammation. Furthermore, anti-inflammatory data was confirmed by X-rays and histological analysis. MOPBS pretreatment did not produce any apparent toxic effect on gastric, kidney and liver function and on muscle strength and motor function. Hence, present data suggest that MOPBS might be a candidate for several chronic inflammatory diseases such RA and other auto-immune diseases