研究SLC-0111:一种碳酸酐酶抑制剂在卡拉胶诱导的大鼠模型中针对环氧化酶介导的炎症途径的抗炎潜力

IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Aslınur Doğan, Elif Merve Betül Yanılmaz, Gulcin Karakoc, Ali Parlar, Ebru Annaç, Nebih Lolak, Suleyman Akocak
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引用次数: 0

摘要

炎症是一种基本的生理反应,导致许多疾病的发展,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酶与碳酸酐酶具有多种结构相似性。SLC-0111是一种以其有效和选择性抑制碳酸酐酶而闻名的分子,尚未研究其对急性炎症、促炎细胞因子水平或氧化应激参数的潜在影响。我们的研究旨在评估SLC-0111与COX酶的结合亲和力,以及其可能的抗炎特性。我们给大鼠SLC-0111分别以50、100和200 mg/kg的剂量治疗3天,然后用卡拉胶(CAR)引起炎症。CAR递送后,每隔4小时评估一次脚掌厚度,以评估炎症水平。此外,用Evans Blue (EB)染料检测了爪组织中的蛋白质外渗。测定足跖组织中丙二醛(MDA)和谷胱甘肽(GSH)水平以评估氧化应激。卡拉胶增强水肿、蛋白外渗和促炎细胞因子TNF-α、IL-1β、IL-6、IL-4和IL-13。SLC-0111降低了除IL-4外的所有这些。同样,我们研究的组织学结果表明,SLC-0111在200 mg/kg的剂量下具有抗炎作用。然而,SLC-0111对MDA和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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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.

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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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