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Background: This study aimed to evaluate oxidative stress parameters in individuals with depression and schizophrenia, considering gender differences, and manifesting suicidal behavior, encompassing thoughts without a tendency to be realized, thoughts with a tendency to be realized, and suicide attempts. Methods: From among the patients from Department of Psychiatry 120 individuals were selected who met the inclusion criteria and did not meet the exclusion criteria for the study. In the initial phase of the project, patients eligible for the study underwent the M.I.N.I 7.0.2 questionnaire (Mini International Neuropsychiatric Interview). Subsequently, in the second phase of the research, venous blood samples were collected from the patients for the purpose of conducting biochemical assessments, focusing on oxidative stress parameters. Results: The obtained results suggest that redox biomarkers, namely TOS (total oxidation state) and OSI (TOS/TAC ratio), in the blood plasma of women increase in tandem with the severity of suicidal behavior. No notable alterations in SOD (Cu-Zn-superoxide dismutase), GPx (glutathione peroxidase), and GSH (reduced glutathione) concentrations and activity were noted between groups exhibiting suicidal behavior. The observed variations in the concentrations and activity of antioxidant parameters were significant solely in comparison to the control group. Conclusions: Redox biomarkers TOS and OSI could prove valuable in diagnosing women at a genuine risk of committing suicide. On the other hand, antioxidant parameters - SOD, GPx, and GSH may be instrumental in identifying patients with suicidal behaviors, without specifying their intensity.
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Introduction: Glycoxidative stress is essential for linking glucose disturbances and cardiovascular diseases. Unfortunately, contemporary antidiabetic drugs do not have an antiglycative effect but only lower blood glucose levels. Therefore, there is an intense search for substances that could inhibit protein glycation and prevent diabetic complications. A potential antioxidant activity has been demonstrated with verapamil, a phenylalkylamine derivative belonging to selective calcium channel blockers. Verapamil has a well-established position in cardiology due to its wide range of indications and good safety profile. Nevertheless, the antidiabetic activity of verapamil is still unclear. We are the first to comprehensively evaluate the verapamil's effect on protein glycoxidation using various in vitro and in silico models. Methods: Bovine serum albumin (BSA) was used to assess the rate of glycoxidation inhibition by verapamil. As glycating factors, sugars (glucose, fructose, and ribose) and aldehyde (glyoxal) were used. Chloramine T was used as an oxidizing agent. Aminoguanidine (protein glycation inhibitor) and Trolox (antioxidant) were used as control substances. The biomarkers of oxidation (total thiols, protein carbonyls, advanced oxidation protein products), glycation (Amadori products, ß-amyloid, advanced glycation end products [AGEs]), and glycoxidation (tryptophan, kynurenine, N-formylkynurenine, dityrosine) were evaluated using colorimetric and fluorimetric methods. The mechanism of antiglycative activity of verapamil was assessed using in silico docking to study its interaction with BSA, glycosidases, and seventeen AGE pathway proteins. Results: In all in vitro models, biomarkers of protein glycation, oxidation, and glycoxidation were significantly ameliorated under the influence of verapamil. The glycoxidation inhibition rate by verapamil is comparable to that of potent antiglycating agents and antioxidants. The molecular docking simulations showed that verapamil bound preferentially to amino acids prone to glycoxidative damage out of an α-glucosidase's active center. Among all AGE pathway proteins, verapamil was best docked with the Janus kinase 2 (JAK2) and nuclear factor-κB (NF-κB). Discussion: The results of our study confirm the antiglycoxidant properties of verapamil. The drug's action is comparable to recognized substances protecting against oxidative and glycation modifications. Verapamil may be particularly helpful in patients with cardiovascular disease and concomitant diabetes. Studies in animal models and humans are needed to confirm verapamil's antiglycative/antidiabetic activity.
