Nesterowicz Miłosz, Żendzian-Piotrowska Małgorzata, Ładny Jerzy Robert, Zalewska Anna, Maciejczyk Mateusz
Students' Scientific Club "Biochemistry of Civilization Diseases" at the Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Białystok, Poland.
Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Białystok, Poland.
Cell Physiol Biochem. 2023 Mar 29;57(2):82-104. doi: 10.33594/000000617.
BACKGROUND/AIMS: Trazodone is a selective serotonin reuptake inhibitor; however, other mechanisms of the drug's anti-depressive properties have also been postulated. Hence, the aim of the study was to perform a systematic review and assess antiglycoxidative properties of trazodone in in vitro models.
Trazodone's scavenging and chelating properties were measured with spectrophotometric method. The impact of the drug on carbonyl/oxidative stress was marked in the bovine serum albumin (BSA) model where sugars (glucose, fructose, galactose, ribose) and aldehydes (glyoxal and methylglyoxal) were used as glycation agents. Aminoguanidine and N-acetylcysteine (NAC) were applied as reference glycation/free radical inhibitors. Glycation biomarkers (kynurenine, N-formylkynurenine, dityrosine as well as advanced glycation end products contents) were assessed spectrofluorometrically. Concentrations of oxidation parameters (total thiols (TTs), protein carbonyls (PCs) and also advanced oxidation protein products (AOPPs) levels) were determined spectrophotometrically.
We demonstrated that trazodone poorly scavenged radicals (hydroxyl radical, nitric oxide, hydrogen peroxide and 2,2-diphenyl-1-picrylhydrazyl radical) and showed low ferrous ion chelating, unlike aminoguanidine and NAC. Sugars/aldehydes caused enhancement of glycation parameters, as well as a decrease of TTs and an increase of PCs and AOPPs levels compared to BSA incubated alone. Trazodone did not reduce oxidation parameters to the baseline (BSA) and significantly exacerbated glycation markers in comparison with both BSA and BSA+glycators. The content of glycation products was markedly lower in aminoguanidine and NAC than in trazodone. The molecular docking of trazodone to BSA revealed its very low affinity, which may indicate non-specific binding of trazodone, facilitating the attachment of glycation factors.
According to our findings, it may be concluded that trazodone poorly counteracts oxidation and intensifies glycation in vitro. A possible mechanism for antiglycoxidative effect of trazodone in vivo may be the enhancement of the body's adaptive response, as indicated by the results of our systematic review.
背景/目的：曲唑酮是一种选择性5-羟色胺再摄取抑制剂；然而，该药物抗抑郁特性的其他机制也已被提出。因此，本研究的目的是进行一项系统评价，并评估曲唑酮在体外模型中的抗糖基化氧化特性。
采用分光光度法测定曲唑酮的清除和螯合特性。在牛血清白蛋白（BSA）模型中标记该药物对羰基/氧化应激的影响，其中糖（葡萄糖、果糖、半乳糖、核糖）和醛（乙二醛和甲基乙二醛）用作糖基化剂。氨基胍和N-乙酰半胱氨酸（NAC）用作参考糖基化/自由基抑制剂。采用荧光分光光度法评估糖基化生物标志物（犬尿氨酸、N-甲酰犬尿氨酸、二酪氨酸以及晚期糖基化终产物含量）。采用分光光度法测定氧化参数（总巯基（TTs）、蛋白质羰基（PCs）以及晚期氧化蛋白产物（AOPPs）水平）的浓度。
我们证明，与氨基胍和NAC不同，曲唑酮清除自由基（羟基自由基、一氧化氮、过氧化氢和2,2-二苯基-1-苦基肼自由基）的能力较差，且亚铁离子螯合能力较低。与单独孵育的BSA相比，糖/醛导致糖基化参数增加，以及TTs减少和PCs及AOPPs水平增加。与BSA和BSA+糖基化剂相比，曲唑酮未将氧化参数降低至基线水平（BSA），且显著加剧了糖基化标记物。氨基胍和NAC中的糖基化产物含量明显低于曲唑酮。曲唑酮与BSA的分子对接显示其亲和力非常低，这可能表明曲唑酮的非特异性结合，促进了糖基化因子的附着。
根据我们的研究结果，可以得出结论，曲唑酮在体外对抗氧化的能力较差，并会加剧糖基化。正如我们系统评价的结果所示，曲唑酮在体内产生抗糖基化氧化作用的一种可能机制可能是增强机体的适应性反应。
