Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection

Author:

Belenichev Igor1,Popazova Olena2ORCID,Bukhtiyarova Nina3,Savchenko Dmytro4,Oksenych Valentyn5ORCID,Kamyshnyi Oleksandr6ORCID

Affiliation:

1. Department of Pharmacology and Medical Formulation with Course of Normal Physiology, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, Ukraine

2. Department of Histology, Cytology and Embryology, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, Ukraine

3. Department of Clinical Laboratory Diagnostics, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, Ukraine

4. Department of Pharmacy and Industrial Drug Technology, Bogomolets National Medical University, 01601 Kyiv, Ukraine

5. Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway

6. Department of Microbiology, Virology and Immunology, I. Horbachevsky Ternopil State Medical University, 46001 Ternopil, Ukraine

Abstract

Despite the significant progress in the fields of biology, physiology, molecular medicine, and pharmacology; the designation of the properties of nitrogen monoxide in the regulation of life-supporting functions of the organism; and numerous works devoted to this molecule, there are still many open questions in this field. It is widely accepted that nitric oxide (•NO) is a unique molecule that, despite its extremely simple structure, has a wide range of functions in the body, including the cardiovascular system, the central nervous system (CNS), reproduction, the endocrine system, respiration, digestion, etc. Here, we systematize the properties of •NO, contributing in conditions of physiological norms, as well as in various pathological processes, to the mechanisms of cytoprotection and cytodestruction. Current experimental and clinical studies are contradictory in describing the role of •NO in the pathogenesis of many diseases of the cardiovascular system and CNS. We describe the mechanisms of cytoprotective action of •NO associated with the regulation of the expression of antiapoptotic and chaperone proteins and the regulation of mitochondrial function. The most prominent mechanisms of cytodestruction—the initiation of nitrosative and oxidative stresses, the production of reactive oxygen and nitrogen species, and participation in apoptosis and mitosis. The role of •NO in the formation of endothelial and mitochondrial dysfunction is also considered. Moreover, we focus on the various ways of pharmacological modulation in the nitroxidergic system that allow for a decrease in the cytodestructive mechanisms of •NO and increase cytoprotective ones.

Publisher

MDPI AG

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