Doğan Aslınur, Yanılmaz Elif Merve Betül, Karakoc Gulcin, Parlar Ali, Annaç Ebru, Lolak Nebih, Akocak Suleyman
Department of Pharmacology, Faculty of Pharmacy, Adıyaman University, Adıyaman, Türkiye.
Department of Veterinary Medicine, Kâhta Vocational School, Adıyaman University, Adıyaman, Türkiye.
J Biochem Mol Toxicol. 2025 Mar;39(3):e70217. doi: 10.1002/jbt.70217.
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.
炎症是一种基本的生理反应，会引发许多疾病，包括组织损伤、哮喘、糖尿病、动脉粥样硬化、炎症性肠病和癌症。COX酶是炎症过程中的重要介质。有趣的是，COX酶与碳酸酐酶在结构上有多个相似之处。SLC - 0111是一种以强效和选择性抑制碳酸酐酶而闻名的分子，但其对急性炎症、促炎细胞因子水平或氧化应激参数的潜在影响尚未得到研究。我们的研究旨在评估SLC - 0111与COX酶的结合亲和力及其可能的抗炎特性。在用角叉菜胶（CAR）引发炎症前3天，我们以50、100和200mg/kg的剂量给大鼠注射SLC - 0111。注射CAR后，每隔4小时评估爪厚度以评估炎症水平。此外，还使用伊文思蓝（EB）染料检测爪组织中的蛋白质外渗情况。测量爪组织中丙二醛（MDA）和谷胱甘肽（GSH）水平以评估氧化应激。角叉菜胶会加重水肿、蛋白质外渗以及促炎细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-4（IL-4）和白细胞介素-13。SLC - 0111除了对IL - 4没有影响外，降低了所有这些指标。同样，我们研究的组织学结果表明，SLC - 0111在200mg/kg的剂量下具有抗炎作用。然而，SLC - 0111对MDA或GSH水平没有显著影响。这些数据表明SLC - 0111可能具有抗炎特性，可用于治疗炎症相关疾病。
