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缬沙坦的多效性特性:它们是否源自抗糖基化活性?文献综述与研究。

Pleiotropic Properties of Valsartan: Do They Result from the Antiglycooxidant Activity? Literature Review and Study.

机构信息

Students Scientific Club "Biochemistry of Civilization Diseases" at the Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, 2c Mickiewicza Street, 15-233 Białystok, Poland.

Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, 2c Mickiewicza Street, 15-233 Białystok, Poland.

出版信息

Oxid Med Cell Longev. 2021 Mar 3;2021:5575545. doi: 10.1155/2021/5575545. eCollection 2021.

Abstract

Valsartan belongs to angiotensin II type 1 (AT1) receptor blockers (ARB) used in cardiovascular diseases like heart failure and hypertension. Except for its AT1-antagonism, another mechanism of drug action has been suggested in recent research. One of the supposed actions refers to the positive impact on redox balance and reducing protein glycation. Our study is aimed at assessing the antiglycooxidant properties of valsartan in an model of oxidized bovine serum albumin (BSA). Glucose, fructose, ribose, glyoxal (GO), methylglyoxal (MGO), and chloramine T were used as glycation or oxidation agents. Protein oxidation products (total thiols, protein carbonyls (PC), and advanced oxidation protein products (AOPP)), glycooxidation products (tryptophan, kynurenine, N-formylkynurenine, and dityrosine), glycation products (amyloid- structure, fructosamine, and advanced glycation end products (AGE)), and albumin antioxidant activity (total antioxidant capacity (TAC), DPPH assay, and ferric reducing antioxidant power (FRAP)) were measured in each sample. In the presence of valsartan, concentrations of protein oxidation and glycation products were significantly lower comparing to control. Moreover, albumin antioxidant activity was significantly higher in those samples. The drug's action was comparable to renowned antiglycation agents and antioxidants, e.g., aminoguanidine, metformin, Trolox, N-acetylcysteine, or alpha-lipoic acid. The conducted experiment proves that valsartan can ameliorate protein glycation and oxidation in various conditions. Available animal and clinical studies uphold this statement, but further research is needed to confirm it, as reduction of protein oxidation and glycation may prevent cardiovascular disease development.

摘要

缬沙坦属于血管紧张素 II 型 1(AT1)受体阻滞剂(ARB),用于心力衰竭和高血压等心血管疾病。除了其 AT1 拮抗作用外,最近的研究还提出了药物作用的另一种机制。其中一种作用是对氧化还原平衡和减少蛋白质糖基化产生积极影响。我们的研究旨在评估缬沙坦在氧化牛血清白蛋白(BSA)模型中的抗糖基化氧化作用。葡萄糖、果糖、核糖、乙二醛(GO)、甲基乙二醛(MGO)和氯胺 T 被用作糖基化或氧化试剂。蛋白质氧化产物(总巯基、蛋白羰基(PC)和晚期氧化蛋白产物(AOPP))、糖基化产物(色氨酸、犬尿氨酸、N-甲酰犬尿氨酸和二酪氨酸)、糖化产物(淀粉样结构、果糖胺和晚期糖基化终产物(AGE))和白蛋白抗氧化活性(总抗氧化能力(TAC)、DPPH 测定和铁还原抗氧化能力(FRAP))在每个样品中进行了测量。在缬沙坦存在下,与对照相比,蛋白质氧化和糖基化产物的浓度显著降低。此外,这些样品中的白蛋白抗氧化活性显著更高。该药物的作用可与著名的抗糖化剂和抗氧化剂相媲美,例如氨基胍、二甲双胍、Trolox、N-乙酰半胱氨酸或α-硫辛酸。进行的实验证明,缬沙坦可以改善各种条件下的蛋白质糖基化和氧化。现有的动物和临床研究支持这一说法,但需要进一步研究来证实这一点,因为减少蛋白质氧化和糖基化可能会预防心血管疾病的发展。

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