Singla Shivani, Kumar Vinod, Jena Gopabandhu
Facility for Risk Assessment and Intervention Studies, Dept. of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Chandigarh, Punjab, 160062, India.
High Resolution Transmission Electron Microscopy Facility, Dept. of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Chandigarh, Punjab, 160062, India.
Biochimie. 2023 Aug;211:96-109. doi: 10.1016/j.biochi.2023.03.009. Epub 2023 Mar 17.
Diabetes and ulcerative colitis are chronic diseases associated with inflammation, dysbiosis, impaired immune function and infection risk. In patients with type 1 diabetes enteropathy, gastrointestinal manifestations are seen relatively frequently. The current investigation was aimed to decipher the role of 3-aminobenzamide (3-AB) in ulcerative colitis associated Diabetes mellitus in male BALB/c mice. Ulcerative colitis associated Diabetes mellitus experimental murine model was developed by 3 cycles (each cycle consists of seven days) of Dextran Sulphate Sodium (DSS; 2.5 %w/v) with recovery time of one week in-between along with Streptozotocin (STZ; 40 mg/kg; i.p. x 5 days; consecutively) was given at the I recovery period. As an intervention, 3-aminobenzamide (3-AB; 5 and 10 mg/kg; intraperitoneally) was given beginning with the second DSS cycle and then continue till sacrifice. 3-aminobenzamide treatment significantly reduced the severity of colitis-associated diabetes mellitus by altering the expression of a number of molecular targets, including sirtuin 1 (SIRT 1), proliferating cell nuclear antigen (PCNA), poly[ADP-ribose] polymerase 1 (PARP-1), cysteine protease-1 (Caspase-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NFkBp65), NLR family pyrin domain containing 3 (NLRP3), insulin growth factor 1 (IGF-1), interleukin-1β (IL-1β), interleukin-10 (IL-10) and β-catenin. Further, 3-AB at high dose (10 mg/kg; intraperitoneally) significantly restored the epithelial tight junction integrity as evaluated by TEM analysis and restored occludin expression analysed by immunofluorescence analysis. Present study revealed that the high dose of 3-AB (10 mg/kg; intraperitoneally) showed significant and consistent protective effects against colitis associated Diabetes mellitus by modulating various molecular targets.
糖尿病和溃疡性结肠炎是与炎症、微生物群失调、免疫功能受损及感染风险相关的慢性疾病。在1型糖尿病肠病患者中，胃肠道表现相对常见。本研究旨在阐明3-氨基苯甲酰胺（3-AB）在雄性BALB/c小鼠溃疡性结肠炎相关性糖尿病中的作用。通过3个周期（每个周期7天）的硫酸葡聚糖钠（DSS；2.5%w/v）构建溃疡性结肠炎相关性糖尿病实验小鼠模型，每个周期之间有1周的恢复时间，在第1个恢复期间连续5天腹腔注射链脲佐菌素（STZ；40mg/kg）。作为干预措施，从第2个DSS周期开始腹腔注射3-氨基苯甲酰胺（3-AB；5和10mg/kg），然后持续至处死。3-氨基苯甲酰胺治疗通过改变包括沉默调节蛋白1（SIRT 1）、增殖细胞核抗原（PCNA）、聚[ADP-核糖]聚合酶1（PARP-1）、半胱氨酸蛋白酶-1（Caspase-1）、活化B细胞核因子κB轻链增强子（NFkBp65）、NLR家族含pyrin结构域蛋白3（NLRP3）、胰岛素生长因子1（IGF-1）、白细胞介素-1β（IL-1β）、白细胞介素-10（IL-10）和β-连环蛋白在内的多个分子靶点的表达，显著降低了结肠炎相关性糖尿病的严重程度。此外，高剂量（10mg/kg；腹腔注射）的3-AB通过透射电镜分析评估，显著恢复了上皮紧密连接的完整性，并通过免疫荧光分析恢复了闭合蛋白的表达。本研究表明，高剂量的3-AB（10mg/kg；腹腔注射）通过调节各种分子靶点，对结肠炎相关性糖尿病显示出显著且一致的保护作用。
