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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, β-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.

Ovarian cancer (OC) has emerged as the leading cause of death due to gynecological malignancies among women. Oxidative stress and metalloproteinases (MMPs) have been shown to influence signaling pathways and afflict the progression of carcinogenesis. Therefore, the assessment of matrix-remodeling and oxidative stress intensity can determine the degree of cellular injury and often the severity of redox-mediated chemoresistance. The study group comprised 27 patients with serous OC of which 18% were classified as Federation of Gynecology and Obstetrics (FIGO) stages I/II, while the rest were diagnosed grades III/IV. The control group comprised of 15 ovarian tissue samples. The results were compared with genetic data from The Cancer Genome Atlas. Nitro-oxidative stress, inflammation and apoptosis biomarkers were measured colorimetrically/fluorometrically or via real-time PCR in the primary ovarian tumor and healthy tissue. Stratification of patients according to FIGO stages revealed that high-grade carcinoma exhibited substantial alterations in redox balance, including the accumulation of protein glycoxidation and lipid peroxidation products. TCGA data demonstrated only limited prognostic usefulness of the studied genes. In conclusion, high-grade serous OC is associated with enhanced tissue oxidative/nitrosative stress and macromolecule damage that could not be overridden by the simultaneously augmented measures of antioxidant defense. Therefore, it can be assumed that tumor cells acquire adaptive mechanisms that enable them to withstand the potential toxic effects of elevated reactive oxygen species.