Aim to assess the activity of superoxide dismutase in erythrocytes of rats after a single intramuscular injection of naphazoline in radiofrequency dose and in experimental simulation of acute radiation sickness. Material and methods. The activity of erythrocytes superoxide dismutase (SOD) after single intramuscular injection of nafazoline in experimental modeling of acute radiation sickness was investigated. The pharmacological properties and mechanisms of radioprotective action of nafazoline were clarified based on the dynamics of activity of erythrocytes SOD in intact and irradiated animals with the dose of 7,4 Gy. Results. The superoxide dismutase activity was found to increase significantly 60 min after single intramuscular administration of nafazolin at a dose of 5 mg/kg. Under experimental conditions of acute radiation disease modeling, a decrease in superoxide dismutase activity was observed within the first hour after exposure, evidencing the direct involvement of the antioxidant system components in the inactivation of free-radical reaction products. Conclusion. The radioprotective properties of naphazoline may be due not only to reduction of oxygen delivery to the cells of radiosensitive tissues and inhibition of their metabolism by effect on 2-adreno- and imidazoline receptors, but also by activation of antioxidant system links.
The forecast of naphazoline pharmacological properties has been made using the PASS computer program and the ADVER-Pred web resource of the Way2Drug information and computing platform. Biological activity, mechanisms of action, toxic and side effects, as well as other types of activity of the studied drug associated with interaction with antitargets, metabolism and gene expression regulation have been determined. The results of the naphazoline pharmacological properties forecast obtained in silico have been compared with the information available in the literature about its systemic effects in clinical use and poisoning.It has been established that the studied chemical compound has a very wide spectrum of action, which is primarily associated with the stimulation of adrenoreceptors and imidazoline receptors located in many organs and tissues of the body. At the same time, other mechanisms of naphazoline action forecasted in silico allow us to determine possible directions for further research of its clinical use. Among the toxic and side effects, along with such known adverse events as effect on the central nervous system and arterial hypertension, in the clinical use of naphazoline special attention should be paid to the cardio-, hepato- and nephrotoxic effects forecasted with a high degree of probability. The prominent toxic effect of naphazoline can cause the occurrence of life- threatening conditions - acute cerebrovascular disorder, myocardial infarction, cardiac rhythm disorders, acute left ventricular failure. The obtained data confirm that the use of modern computer methods that provide an assessment of biological activity based on the drug-like compound graphic formula allows us to obtain a forecast with a high degree of confidence for both new pharmacological substances and for drugs approved for clinical use in order to clarify their pharmacological properties.
This paper presents the summarized information on the mechanisms of neuroimmunoendocrine organism reaction to external adverse impacts (irrespective of their etymology), and on the key elements in these reactions development. It is found that adverse external factors are responsible for a change of an organisms functional state, involving neuroendocrinal and immune systems in the (stress) reaction formation. Neuroendocrinal and immune systems act like coordinators of the intersystemic and interorgan relations in the setting of both adaptive and pathological processes. The combination of feed-forward and feedback (positive and negative) connections controlled by hormones, neuromediators, neuropeptides, cytokines and their corresponding receptors, serves as the basis of neuroendocrinal and immune systems interaction. Through mediators and hormones, the neuroendocrinal system modulates the immune system, and the latter can modulate functions of the former due to its cytokine network. Along with humoral mechanisms, the vagal nerve which enables the reflectory control of immunity, is the key component of the system providing the functional unity of nervous and immune system. The conversion of immune signals to neural ones is done through activation of vagal afferent fibers by proinflammatory cytokines, whereas its efferent fibers, forming the cholinergic anti-inflammatory pathway, ensure the descending central nervous system effects which prevent the hyperactivation of innate and adaptive immune reactions. The body balance control is based on the integrative activity of nervous, endocrinal and immune systems both under normal and pathological conditions (traumas, infections, stress, physical and chemical exposures, etc). The systematization of information about the coordinated neuroimmunoendocrine interaction provides background for theoretical underpinning of the upcoming trends in search of means and ways to correct the negative influence of adverse external factors on a living organism.
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