Agomelatine's antiglycoxidative action—In vitro and in silico research and systematic literature review

Abstract

IntroductionAgomelatine is an atypical antidepressant drug enhancing norepinephrine and dopamine liberation; nevertheless, additional mechanisms are considered for the drug's pharmacological action. Since protein glycoxidation plays a crucial role in depression pathogenesis, agomelatine's impact on carbonyl/oxidative stress was the research purpose.MethodsReactive oxygen species scavenging (hydroxyl radical, hydrogen peroxide, and nitrogen oxide) and antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion chelating assays) of agomelatine were marked. Agomelatine's antiglycoxidation properties were assayed in sugars (glucose, fructose, and galactose) and aldehydes- (glyoxal and methylglyoxal) glycated bovine serum albumin (BSA). Aminoguanidine and α-lipoic acid were used as standard glycation/oxidation inhibitors.ResultsAgomelatine did not show meaningful scavenging/antioxidant capacity vs. standards. Sugars/aldehydes increased glycation (↑kynurenine, ↑N-formylkynurenine, ↑dityrosine, ↑advanced glycation end products, and ↑β-amyloid) and oxidation (↑protein carbonyls and ↑advanced oxidation protein products) parameters in addition to BSA. Standards restored BSA baselines of glycation and oxidation markers, unlike agomelatine which sometimes even intensifies glycation above BSA + glycators levels. Molecular docking analysis of agomelatine in BSA demonstrated its very weak binding affinity.DiscussionAgomelatine's very low affinity to the BSA could proclaim non-specific bonding and simplify attachment of glycation factors. Thereby, the drug may stimulate brain adaptation to carbonyl/oxidative stress as the systematic review indicates. Moreover, the drug's active metabolites could exert an antiglycoxidative effect.

Novel Properties of Old Propranolol─Assessment of Antiglycation Activity through In Vitro and In Silico Approaches

“…Exact concentrations of glycation agents and specific, optimal incubation conditions were determined and validated in compliance with the outcome of the previous kinetic studies. 19 − 25 Despite this, the concentrations of oxidants, sugars, and aldehydes were substantially higher than the physiological reference values. They are instrumental in modeling the physiological processes that occur in the human body over weeks or even months in a notably short time.…”

“…In order to differentiate the results obtained for propranolol, aminoguanidine as a known protein oxidation inhibitor and captopril as an established antioxidant were utilized. Exact concentrations of glycation agents and specific, optimal incubation conditions were determined and validated in compliance with the outcome of the previous kinetic studies. − Despite this, the concentrations of oxidants, sugars, and aldehydes were substantially higher than the physiological reference values. They are instrumental in modeling the physiological processes that occur in the human body over weeks or even months in a notably short time. ,, These conditions are routinely applied to determine the antiglycation properties of new substances. ,,− All the additives (1 mM) had their concentration determined in compliance with the outcome of other in vitro studies, in proportion to the high concentrations of the glycating agents. − The study was conducted in three series, each duplicated.…”

“…In addition, aldehydes, glyoxal (GO), and methylglyoxal (MGO) were utilized. BSA was incubated with propranolol (1 mM) as well as 0.5 M of Glc, Fru, and Gal for 6 days or GO and MGO (2.5 mM) for a period of 12 h. − ,− GO and MGO were utilized within a month after delivery, and working solutions were assembled briefly before assessment. In order to study the antioxidant properties of propranolol, BSA with propranolol was incubated with 20 mM of chloramine T (ChT) for 1 h .…”

“…Glycation/oxidation of BSA was performed based on previously applied methods. − BSA (98% purity) was immediately dissolved in 0.1 M sodium phosphate buffer (pH 7.4) that contained a preservative of 0.02% sodium azide. The following glycation agents were used: glucose (Glc), fructose (Fru), and galactose (Gal).…”

Antioxidant and Anti-Glycation Potential of H2 Receptor Antagonists—In Vitro Studies and a Systematic Literature Review

“…The samples were diluted with 0.1 M sulfuric acid (1:5, v : v ) before the measurements. The results were standardized to the fluorescence of 0.1 mg/mL of quinine sulfate in 0.1 M sulfuric acid [ 66 ].…”