Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching at different temperatures and data obtained from the van’t Hoff diagram and molecular docking indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site for all drugs in the central cavity near αβ interfaces and is dominantly mediated through hydrophobic forces. The association constants were lower-moderate strength (~10⁴ M⁻¹), the highest observed for clozapine (2.2 × 10⁴ M⁻¹ at 25 °C). The clozapine binding showed “friendly” effects: increased α-helical content, a higher melting point, and protein protection from free radical-mediated oxidation. On the other hand, bound ziprasidone and sertindole had a slightly pro-oxidative effect, increasing ferrihemoglobin content, a possible “foe”. Since the interaction of proteins with drugs plays a vital role in their pharmacokinetic and pharmacodynamic properties, the physiological significance of the obtained findings is briefly discussed.

This study examined alterations in serum redox biomarkers before and one month after administration of the coronavirus disease 2019 (COVID-19) booster (third) doses across four vaccine regimens. A longitudinal cohort of 410 adults was analyzed following homologous Pfizer-BioNTech, Sinopharm [Vero Cell]-Inactivated, Sputnik V, or heterologous Sinopharm/Pfizer vaccination. Serum total proteins, albumin, total thiols, nitrites, ferric-reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity were measured, with DPPH interpreted as an ex vivo surrogate of serum radical-scavenging capacity. Additional analyses included stratification by prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, multivariable regression, correlation analysis, effect-size estimation, and sensitivity testing. Booster vaccination was associated with modest but consistent decreases in DPPH activity, albumin, and total proteins, whereas FRAP, nitrite, and total thiol levels remained stable. This pattern supports a transient shift in antioxidant buffering capacity but, by itself, does not exclude oxidative stress, as direct oxidative damage markers were not assessed. The most pronounced changes were observed in Sinopharm-based regimens, particularly in the heterologous Sinopharm/Pfizer group. Prior SARS-CoV-2 infection did not materially alter the qualitative response pattern, whereas older age and comorbidities were associated with greater declines in DPPH activity and albumin. Overall, the findings indicate a modest, transient redox-associated response following booster-induced immune activation and suggest that host-related factors, such as age and comorbidity burden, may accentuate short-term changes in antioxidant buffering capacity.

Klinefelter syndrome (KS) is the most frequent type of congenital sex-chromosomal disorder caused by at least one extra X chromosome and commonly treated with lifetime testosterone therapy. Ulcerative lesions on lower extremities may occur as a complication of KS. The pathogenesis of ulcers in KS patients has not been clarified on a molecular level. Here we present a case of leg ulcers exacerbation associated with the administration of a high dose of acetylsalicylic acid in a 63-year-old KS patient with karyotype 47,XXY undergoing testosterone replacement therapy for the last 20 years. The appearance of the ulcer on the patient's leg occurred during one week of high oral acetylsalicylic acid intake (1.2 g daily). The patient was advised to return to his standard daily dose of 0.1 g of acetylsalicylic acid and significant improvement of his leg ulcer was observed after two weeks. We hypothesize that testosterone-mediated nitric oxide balance in KS patient is perturbed under the condition of acute high-dose acetylsalicylic acid administration. We propose that small standard doses of approximately 0.1 g/day of acetylsalicylic acid have no apparent effect on nitric oxide status, whereas higher doses may cause dysregulation of nitric oxide production and/or utilization, creating conditions which may cause the appearance of leg ulcers in the KS patients.