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Valeriana PANTEA, Ecaterina PAVLOVSCHI, Aurelian GULEA, Silvia STRATULAT, Svetlana PROTOPOP, Vasile MACARI, Olga TAGADIUC and Valentin GUDUMAC; The influence of thiosemicarbazone derivatives on total nitric oxide levels and endothelial nitric oxide synthase activity: A sex-dependent comparative study; Proceedings of NanoBioMat 2025(2): 78-91
THE INFLUENCE OF THIOSEMICARBAZONE DERIVATIVES ON TOTAL NITRIC OXIDE LEVELS AND ENDOTHELIAL NITRIC OXIDE SYNTHASE ACTIVITY: A SEX-DEPENDENT COMPARATIVE STUDY
Valeriana PANTEA1*, Ecaterina PAVLOVSCHI2, Aurelian GULEA3, Silvia STRATULAT2, Svetlana PROTOPOP2, Vasile MACARI4, Olga TAGADIUC2 and Valentin GUDUMAC1
1 The Laboratory of biochemistry, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova;
2 Chair of Biochemistry and Clinical Biochemistry, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova;
3The Laboratory of Advanced Materials in Biopharmaceutics and Technology, State University of Moldova, Chisinau, Republic of Moldova;
4Technical University of Moldova, Department of Food Safety and Public Health, Chisinau, Republic of Moldova
* Correspondence: valeriana.pantea@usmf.md
ABSTRACT
Background. Thiosemicarbazones are organic compounds with high pharmacological potential, recognized for their ability to form stable complexes with various metal ions. In particular, copper–thiosemicarbazone complexes have garnered increasing interest due to their significant biological activities, including antimicrobial, antioxidant, and antitumor effects. These complexes exhibit high chemical stability and enhanced interaction with biomolecules, positioning them as promising candidates for the development of novel therapeutic agents.
Objective of the study. The aim of this study was to investigate the effects of copper–thiosemicarbazone coordination compounds (CuCCTs) on nitric oxide (NO) concentration and endothelial nitric oxide synthase (eNOS) activity in erythrocytes, using an in vivo experimental model.
Material and Methods. This study evaluated the impact of CuCCT administration in 120 rats, distributed into 10 experimental groups and divided by sex into two subgroups: (a) males and (b) females. Animals in the control group (Group 1) received subcutaneous injections of physiological saline. In the treatment groups (Groups 2–10: CMA-18, CMD-8, MG-22, CMC-34, CMJ-33, CMT-67, CMG-41, TIA-123, and TIA-160), CuCCTs were administered subcutaneously at a dose of 10 µg/kg daily for 30 days.
Results. Evaluation of total NO levels revealed non-significant variations across compounds and between sexes. The most notable enhancement was observed with the benzothiazole-based compound CMA-18, particularly in females, who showed a 23% elevation compared to controls. Overall, female rats exhibited higher NO levels than their male counterparts. These findings suggest a sex-dependent and structure-specific response to treatment, which may be exploitable in the design of targeted pharmacological strategies. Endothelial nitric oxide synthase (eNOS) activity, expressed as µM/g·Hb, was compared to the control group. Significant increases in eNOS activity were observed in females treated with MG-22 and CMG-41, reaching up to 39% enhancement (p < 0.05). In contrast, male rats showed minimal or no changes in eNOS activity. These results underscore a sex-dependent effect influenced by the chemical structure of the compounds and highlight their therapeutic potential in cardiovascular conditions.
Conclusion. Thiosemicarbazone derivatives modulate nitric oxide concentration and eNOS activity in a sex- and structure-dependent manner, with significant stimulation observed in females. These compounds represent promising candidates for the development of personalized cardiovascular therapies
Keywords: erythrocytes, copper coordination compounds with thiosemicarbazones, NO, eNOS