Investigating the Anti-Inflammatory Potential of SLC-0111: A Carbonic Anhydrase Inhibitor Targeting Cyclooxygenase-Mediated Inflammatory Pathways in a Carrageenan-Induced Rat Model

Abstract

Inflammation is a fundamental physiological reaction that leads to the development of many diseases, including tissue damage, asthma, diabetes, atherosclerosis, inflammatory bowel disease, and cancer. The enzyme COX is a vital mediator in inflammatory processes. Interestingly, the COX enzyme possesses multiple structural similarities to the carbonic anhydrase enzyme. SLC-0111, a molecule known for its potent and selective inhibition of carbonic anhydrase, has not yet been studied for its potential effects on acute inflammation, proinflammatory cytokine levels, or oxidative stress parameters. Our study seeks to assess the binding affinity of SLC-0111 to the COX enzyme, as well as its possible anti-inflammatory properties. We treated rats SLC-0111 at dosages of 50, 100, and 200 mg/kg for 3 days before generating inflammation with carrageenan (CAR). Following CAR delivery, paw thickness was evaluated at 4-h intervals to assess inflammatory levels. Additionally, protein extravasation in paw tissue has been examined using Evans Blue (EB) dye. MDA and glutathione (GSH) levels in paw tissue were measured to assess oxidative stress. Carrageenan enhanced edema, protein extravasation, and proinflammatory cytokines TNF-α, IL-1β, IL-6, IL-4, and IL-13. SLC-0111 decreased all of these, except for IL-4. Similarly, the histological findings of our research indicated that SLC-0111 had an anti-inflammatory effect at a dose of 200 mg/kg. However, SLC-0111 had no significant effect on MDA or GSH levels. These data represent that SLC-0111 may have anti-inflammatory properties and could be used as a treatment for inflammation-related disorders.