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

Kacper Maksymilian Mil,Anna Zalewska,Cezary Pawlukianiec,Małgorzata Żendzian-Piotrowska,Małgorzata Ewa Gryciuk,Mateusz Maciejczyk,Jerzy Robert Ładny,Gaetano Santulli

doi:10.1155/2021/5575545

Kacper Maksymilian Mil, Anna Zalewska + Show 6 more

Open Access

https://doi.org/10.1155/2021/5575545

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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 in vitro 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-β 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 vitro 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.

Highlights

The formation of free radicals is an inevitable consequence of aerobic metabolism
reactive oxygen species (ROS) produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are responsible for nitric oxide (NO) depletion caused by its interaction with superoxide radical anions (O2-)
The addition of glucose to the bovine serum albumin (BSA) solution led to increased protein oxidation products—Protein carbonyls (PC) and advanced oxidation protein products (AOPP)

Summary

Introduction

The formation of free radicals is an inevitable consequence of aerobic metabolism. As long as physiological mechanisms manage to eliminate reactive oxygen species (ROS), their adverse action on structural proteins, enzymes, membrane lipids, or nucleic acids may remain unseen [1]. The generation of ROS may exceed the capability of the organism to neutralize them This situation is called redox imbalance and leads to oxidative damage to cellular biomolecules [2]. ROS produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are responsible for nitric oxide (NO) depletion caused by its interaction with superoxide radical anions (O2-). This results in decreased endothelial nitric oxide synthase (eNOS) activity and leads to endothelial dysfunction, which is considered one of the essential pathogenetic factors [16, 17]. As an effect of this remodeling, stiffness of the vessel and peripheral resistance increase [9]

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