Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Saudi Arabia.
Department of Biosciences, Integral University, Lucknow, India.
Biomed Res Int. 2021 May 12;2021:5591851. doi: 10.1155/2021/5591851. eCollection 2021.
Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes-associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes-associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5-1.0 mmol/L). The HPLC results showed that AG-Gnp fairly hampers the formation of glycation adducts. Moreover, the studies revealed AG-Gnp mediated inhibition in the production of total-AGEs and - -(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG-Gnp-treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs.
蛋白质发生糖基化，导致晚期糖基化终产物（AGEs）的产生，这些产物在糖尿病相关的继发性并发症的发生和发展中起着核心作用。氨基胍（AG）通过抑制活性羰基物质（RCS）如甲基乙二醛（MGO）的生成来充当抗糖基化剂。先前关于 AG 的抗糖基化行为的研究在治疗糖尿病相关的微血管并发症方面取得了有希望的结果，但由于在高浓度（>10mmol/L）下发现它具有毒性而被停止使用。本文旨在通过将金纳米粒子（Gnp）与浓度较低的 AG（0.5-1.0mmol/L）结合来抑制糖基化。HPLC 结果表明，AG-Gnp 相当程度地阻止了糖基化加合物的形成。此外，研究表明，AG-Gnp 介导抑制了糖尿病大鼠模型中总 AGEs 和 - -（羧甲基）赖氨酸（CML）的产生。这种抑制与抗氧化参数、血糖、胰岛素和糖化血红蛋白水平直接相关。此外，AG-Gnp 处理的大鼠的组织病理学显示，与糖尿病大鼠相比，受损的胰腺组织有了较好的恢复。我们提出，这种方法可以在相对较低的浓度下提高 AG 的疗效，以避免毒性，并可能有助于克服抗糖基化药物的危险作用。
