Facility for Risk Assessment and Intervention Studies, Dept. of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Punjab, 160062, S.A.S Nagar, India.
Eur J Pharmacol. 2022 Apr 5;920:174861. doi: 10.1016/j.ejphar.2022.174861. Epub 2022 Feb 24.
Various preclinical and clinical studies reported that Poly [ADP-ribose] polymerase 1 plays significant role in all acute and chronic inflammatory diseases with different etiopathogenesis. The present study aims to investigate the protective effect of 3-aminobenzamide in Dextran Sulphate Sodium induced ulcerative colitis and associated molecular mechanisms. Ulcerative colitis in male BALB/c mice was induced using Dextran sulphate sodium (3 %w/v) for 3 cycles with 7 days recovery period in-between. 3-aminobenzamide was administered at the doses of 5, 10 and 20 mg/kg starting from the I week of remission period and was continued till the termination of the experiment. The effect of 3-aminbenzamide was evaluated using biochemical parameters, histopathological evaluations, ELISA, immunohistochemistry, immunofluorescence and Western blot analysis. All the doses of 3-aminobenzamide (5 mg/kg; 10 mg/kg and 20 mg/kg) ameliorated the severity of ulcerative colitis by modulating various molecular targets such as poly[ADP-ribose] polymerase 1, nuclear factor kappa-light-chain-enhancer of activated B cells, NLR family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, cysteine aspartases, interleukin-1β, proliferating cell nuclear antigen, sirtuin 1, adenosine monophosphate-activated protein kinase, tumour necrosis factor-α and catalase. However, the lower doses (5 and 10 mg/kg) exerted more prominent effects in comparison to the high dose (20 mg/kg). Further, 3-aminobenzamide treatment restored the intestinal integrity by increasing the expression of occludin and significantly ameliorated ulcerative colitis associated elevated lipopolysaccharides, oxidative and nitrosative stress, cellular damage and apoptosis. Lower doses of 3-aminobenzamide showed more prominent protective effects against ulcerative colitis associated damage as compared to higher dose.
各种临床前和临床研究报告称，聚[ADP-核糖]聚合酶 1 在具有不同病因发病机制的所有急性和慢性炎症性疾病中都发挥着重要作用。本研究旨在探讨 3-氨基苯甲酰胺在葡聚糖硫酸钠诱导的溃疡性结肠炎及其相关分子机制中的保护作用。雄性 BALB/c 小鼠采用葡聚糖硫酸钠（3%w/v）诱导溃疡性结肠炎，每 7 天为一个周期，中间有 7 天恢复期。从缓解期的第 1 周开始，以 5、10 和 20mg/kg 的剂量给予 3-氨基苯甲酰胺，并持续至实验结束。通过生化参数、组织病理学评估、ELISA、免疫组化、免疫荧光和 Western blot 分析评估 3-氨基苯甲酰胺的作用。所有剂量的 3-氨基苯甲酰胺（5mg/kg；10mg/kg 和 20mg/kg）通过调节各种分子靶点，如聚[ADP-核糖]聚合酶 1、核因子 kappa-轻链增强子的活性 B 细胞、NLR 家族包含吡啶结构域 3、含半胱氨酸天冬氨酸蛋白酶募集域的凋亡相关斑点样蛋白、半胱氨酸天冬氨酸蛋白酶、白细胞介素-1β、增殖细胞核抗原、SIRT1、腺苷单磷酸激活蛋白激酶、肿瘤坏死因子-α和过氧化氢酶，改善了溃疡性结肠炎的严重程度。然而，与高剂量（20mg/kg）相比，低剂量（5 和 10mg/kg）的效果更为显著。此外，3-氨基苯甲酰胺治疗通过增加紧密连接蛋白的表达，显著改善了溃疡性结肠炎相关的升高的脂多糖、氧化和硝化应激、细胞损伤和细胞凋亡，从而恢复了肠道完整性。与高剂量相比，3-氨基苯甲酰胺的低剂量对溃疡性结肠炎相关损伤表现出更显著的保护作用。
