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

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.

Influence of SGLT2 Inhibitor Treatment on Urine Antioxidant Status in Type 2 Diabetic Patients: A Pilot Study

“…The study performed most recently with another nephroprotective class of drugs-angiotensin II receptor blockers (ARB)-demonstrated their antiglycooxidant activity. These findings support the need for future studies in this area with the use of SGLT2i [63]. Given the fact that some literature reports suggest SGLT2i interact with AGEs during their formation, the next step in future studies could address this matter further [64][65][66].…”

Plasma and Urine Total Antioxidant Capacity in Patients With Adrenal Tumors

“…Nevertheless, the TAC method measures only part of the antioxidant capacity, i.e. nonenzymatic activity [23,42]. In our study we observed diminished plasma TAC in patients with pheochromocytoma.…”

Urinary excretion of amino acids and their advanced glycation end-products (AGEs) in adult kidney transplant recipients with emphasis on lysine: furosine excretion is associated with cardiovascular and all-cause mortality

“…In a type 2 diabetic nephropathy rat model, two anti-hypertensive drugs of different mechanisms of action, i.e., olmesartan and hydralazine, were found to inhibit in vivo formation of protein pentosidine in the kidney and to improve renal damage (Nangaku et al 2003). Analogous results were observed for various AGEs in vivo and in vitro for valsartan (Mil et al 2021; see also Prasad and Mishra 2017).…”