Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland.
Department of Cytobiochemistry, University of Lodz, 90-236 Lodz, Poland.
Int J Mol Sci. 2021 Mar 18;22(6):3121. doi: 10.3390/ijms22063121.
Inflammatory bowel diseases (IBD) are at the top of the worldwide rankings for gastrointestinal diseases as regards occurrence, yet efficient and side-effect-free treatments are currently unavailable. In the current study, we proposed a new concept for anti-inflammatory treatment based on gold (III) complexes. A new gold (III) complex TGS 121 was designed and screened in the in vitro studies using a mouse macrophage cell line, RAW264.7, and in vivo, in the dextran sulphate sodium (DSS)-induced mouse model of colitis. Physicochemical studies showed that TGS 121 was highly water-soluble; it was stable in water, blood, and lymph, and impervious to sunlight. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, the complex showed a potent anti-inflammatory profile, as evidenced in neutral red uptake and Griess tests. In the DSS-induced mouse model of colitis, the complex administered in two doses (1.68 μg/kg, intragastrically, and 16.8 μg/kg, intragastrically, once daily) produced a significant (* < 0.05) anti-inflammatory effect, as shown by macroscopic score. The mechanism of action of TGS 121 was related to the enzymatic and non-enzymatic antioxidant system; moreover, TGS 121 induced changes in the tight junction complexes expression in the intestinal wall. This is the first study proving that gold (III) complexes may have therapeutic potential in the treatment of IBD.
炎症性肠病（IBD）是全球胃肠道疾病中发病率最高的疾病，但目前还没有有效且无副作用的治疗方法。在本研究中，我们提出了一种基于金（III）配合物的抗炎治疗新概念。一种新的金（III）配合物 TGS 121 在体外研究中使用 RAW264.7 小鼠巨噬细胞系和体内葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型进行了设计和筛选。物理化学研究表明，TGS 121 具有高水溶性；它在水中、血液和淋巴中稳定，并且不透光。在脂多糖（LPS）刺激的 RAW264.7 细胞中，该配合物表现出强大的抗炎特性，这在中性红摄取和格里斯测试中得到了证明。在 DSS 诱导的结肠炎小鼠模型中，该配合物以两种剂量（1.68μg/kg，灌胃和 16.8μg/kg，灌胃，每天一次）给药产生了显著的（* < 0.05）抗炎作用，表现在宏观评分上。TGS 121 的作用机制与酶和非酶抗氧化系统有关；此外，TGS 121 诱导了肠壁紧密连接复合物表达的变化。这是第一个证明金（III）配合物在治疗 IBD 方面可能具有治疗潜力的研究。
