Therapeutic Effects of Carbonic Anhydrase II inhibitor on Type II Collagen Induce BALB/c Mice

Abstract

Rheumatoid Arthritis is polyarticular, systematic, inflammatory autoimmune disease with joint destruction. Genetic, environmental factors and underlying RA. Around 0.5 to 1% of the world population is afflicted with the RA. 0.55-0.75% Pakistanis have been suffering from the disease. Prazosin and Sulpiride belong to the class of quinazolinamines and Benzamide autoimmunity are known to trigger the onset and perpetuation of synovitis. The objective of this study is Prazosin and Sulpiride may inhibit the expression of Carbonic Anhydrase II, this should also reduce the pro-inflammatory cytokines to revert the disease status. Prazosin and Sulpiride have also less oxidative stress which also help to remission the disease severity and maintain the pH of synovial joints. A collagen induce arthritis mice model was developed for assessment of pharmacodynamics properties of drugs. Mice group treated with 2 mg/kgBW of Prazosin and 5 mg/kgBW Sulpiride show the significant decrease the inflammation of Hind-paws at second day of treatment and spleen index at day 23 (p <0.005). Histopathological analysis of paws revealed that mice treated with different concentration of drugs shown significant reduction in pathology while reduce the tissue hyperplasia. Radiographs of mice hind-paws at day 22 represent the significant reduction in disease pathogenesis. 2 mg/kgBW and 5 mg/kgBW treated mice group show better therapeutic efficacy as compare to others. The oxidative stress induced by dose dependent manner of Prazosin and Sulpiride was checked by performing the NOS assay. The anti-oxidative properties was shown while compare with LPS induced lymphocytes (p <0.05). Prazosin and Sulpiride mediated inhibition of CAII, MMP9 and TNF-α was shown that 2 mg/kgBW and 5 mg/kgBW Sulpiride significantly inhibit the expression of CAII (p <0.005). MMP9 expression significantly decreased was also observed in mice treated 2 mg/kgBW and 5 mg/kgBW (p <0.005). Similarly, Prazosin and Sulpiride activity was also observed in the inhibition of TNF-α. In case of 2mg/kgBW and 5 mg/kg BW treated mice was significantly decrease in the expression of TNF-α (p <0.05). The current study shows that Prazosin and Sulpiride has potential as an anti-arthritic as well as anti-inflammatory drug due to its inhibitory and anti-oxidative properties.