In Vitro Screening of Potential Carbonic Anhydrase-II inhibitors as Novel Anti-Resorption Therapeutic Agents in Rheumatoid Arthritis

Abstract

Rheumatoid Arthritis is a systemic autoimmune disease characterized by chronic inflammation of joints, destruction of cartilage and autoantibody production. Oxidative stress has been recently implicated in the pathogenesis of Rheumatoid Arthritis and Carbonic Anhydrase II (CA-II) has been identified to be a major part of the nexus of pathophysiological components inducing reactive oxygen species, inflammation and autoimmunity which eventually leads to bone resorption and cartilage destruction. The aim of this project was to identify a novel role for Prazosin and Sulpiride as Carbonic Anhydrase-II inhibitors. This was done via in vitro testing of these inhibitors in MH-7A human arthritic cell line, followed by the evaluation of DNA damage induction and cytotoxicity via Comet Assay and MTT Assay respectively. Post-transcriptional expression levels of CA-II in conjunction with those of TNF-α and MMP-9 were determined via qRT- PCR. Prazosin and Sulpiride were both shown to have noncytotoxic and DNA protective effect on MH-7A cells. At the post-transcriptional level, only Sulpiride effectively downregulated the expression of CA-II. These findings will help potentiate their role as anti-resorptive therapeutic agents and open a new avenue of treatment options available to Rheumatoid Arthritis patients.