背景:组胺H2受体拮抗剂是一组在胃肠道疾病中抑制胃液分泌的药物。然而,有证据表明H2阻断剂具有更广泛的活性.H2阻断剂的抗氧化特性尚未完全阐明,它们的抗糖基化潜力迄今尚未被研究。因此,这是第一项比较最受欢迎的H2拮抗剂(雷尼替丁,西咪替丁,和法莫替丁)对蛋白质的体外氧化作用。方法:使用糖(葡萄糖,果糖,半乳糖,和核糖)以及醛(乙二醛和甲基乙二醛)。结果:在分析的药物组中,在所有测试模型中,雷尼替丁是唯一能显著抑制BSA糖基化的H2阻断剂.蛋白质羰基的含量,蛋白质糖氧化产物(△二酪氨酸,△N-甲酰基犬尿氨酸),与添加糖化剂的BSA相比,添加雷尼替丁的糖化BSA样品中的早期(留给Amadori产品)和晚期(留给AGEs)蛋白糖化产物减少。雷尼替丁的抗糖基化潜力与氨基胍和Trolox相当。在分子对接分析中,雷尼替丁的特征是BSA位点的结合能最低,并且可以与蛋白质氨基竞争羰基的添加。H2阻断剂也清除自由基。在雷尼替丁中发现了最强的抗氧化特性,它还具有结合过渡金属离子的能力。系统的文献综述还表明,雷尼替丁的抗糖基化作用可归因于其抗氧化特性。结论:雷尼替丁具有抗糖基化和抗氧化特性。需要进一步的研究,特别是在患有促进蛋白质糖基化的疾病的患者中。
Background: Histamine H2 receptor antagonists are a group of drugs that inhibit gastric juice secretion in gastrointestinal diseases. However, there is evidence to suggest that H2 blockers have a broader spectrum of activity. The antioxidant properties of H2 blockers have not been fully elucidated, and their anti-glycation potential has not been studied to date. Therefore, this is the first study to compare the antioxidant and antiglycation potentials of the most popular H2 antagonists (ranitidine, cimetidine, and famotidine) on protein glycoxidation in vitro. Methods: Bovine serum albumin (BSA) was glycated using sugars (glucose, fructose, galactose, and ribose) as well as aldehydes (glyoxal and methylglyoxal). Results: In the analyzed group of drugs, ranitidine was the only H2 blocker that significantly inhibited BSA glycation in all tested models. The contents of protein carbonyls, protein glycoxidation products (↓dityrosine, ↓N-formylkynurenine), and early (↓Amadori products) and late-stage (↓AGEs) protein glycation products decreased in samples of glycated BSA with the addition of ranitidine relative to BSA with the addition of the glycating agents. The anti-glycation potential of ranitidine was comparable to those of aminoguanidine and Trolox. In the molecular docking analysis, ranitidine was characterized by the lowest binding energy for BSA sites and could compete with protein amino groups for the addition of carbonyl groups. H2 blockers also scavenge free radicals. The strongest antioxidant properties are found in ranitidine, which additionally has the ability to bind transition metal ions. The systematic literature
review also revealed that the anti-glycation effects of ranitidine could be attributed to its antioxidant properties. Conclusions: Ranitidine showed anti-glycation and antioxidant properties. Further research is needed, particularly in patients with diseases that promote protein glycation.