Citation: Galenko-Yaroshevsky PA, Nefedov DA, Zelenskaya AV, Pavlyuchenko II, Chuyan EN, Ravaeva MY, Tkharkakhova NK (2018) Effects of Dimephosphone on skin survival in conditions of reduced blood circulation. Research Results in Pharmacology 4(4): 41-52. https://doi. AbstractIntroduction: The search for and creation of drugs with dermatoprotective and metabotropic activity is one of the priorities of modern diabetology. Synthetic organophosphorus compounds with no anticholinesterase activity, to which Dimephosphone belongs to, deserve great attention in this respect. Materials and Methods:Experiments included 355 white non-linear male mice (18-34 g) and 799 male rats (150-305 g). The dermatoprotective activity (DPA) of Dimephosphone regarding the survival of a skin graft was studied against the background of normoglycemia, as well as against the background of experimental diabetes complicated by hypercholesterolemia. The study of microhemodynamics in the skin was performed using laser Doppler flowmetry. The effects on metabolic processes and the antioxidant system were studied by determining the levels of glucose, urea, creatinine, total bilirubin, total cholesterol, triglycerides, total protein, albumin, globulin, catalase, malondialdehyde, superoxide dismutase, glutathione reductase, glutathione and glutathione peroxidase.Results: Dimephosphone has a pronounced DPA in conditions of reduced blood circulation against the background of normoglycemia and experimental (alloxan) diabetes complicated by exogenous hypercholesterolemia. By DPA, in most cases against the background of normoglycemia Dimephosphone exceeds Actovegine, is comparable to or inferior to Trental and Mexidol, and is more significant in terms of the therapeutic width than all the drugs taken for comparison.Discussion: According to the obtained data , DPA of Dimephosphone may be due to its ability to exhibit significant vasodilating, antihypoxic, antioxidant, antiaggregant, membrane-stabilizing, anti-acidotic, antimicrobial and other properties and also to exert a normalizing effect on carbohydrate, protein, lipid and energy metabolism Conclusion: Dimephosphone can be recommended for further preclinical and clinical studies in the form of various dosage forms, as well as in a combination therapy for metabolic disorders.
АННОТАЦИЯ Цель. Выявление основных механизмов действия димефосфона на кожную микрогемодинамику. Материалы и методы. Изучение влияния димефосфона на микроциркуляцию крови в коже нелинейных крыс-самцов включало регистрацию показателя перфузии, среднего квадратического отклонения, коэффициента вариации; определение амплитуды колебаний кровотока разных частотных диапазонов (с помощью метода лазерной допплеровской флоуметрии). Результаты. Под влиянием димефосфона происходят изменения осцилляторных и неосцилляторных показателей микрогемодинамики в коже, что свидетельствует об увеличении перфузии периферических тканей и модуляции кровотока в микрососудах за счет повышения функциональной активности эндотелия, снижения периферического сопротивления, увеличения притока крови в нутритивное микрососудистое русло и улучшения венулярного оттока. Заключение. Вазоактивные свойства димефосфона проявляются в его способности влиять на сосудистые и внесосудистые регуляторные процессы микроциркуляции крови в коже. Наиболее чувствительным к действию димефосфона является эндотелий микрососудов и его метаболическая функция, ассоциированная с рилизингом NO. Основным механизмом вазотропного действия димефосфона является его способность усиливать продукцию NO эндотелием, что влечет за собой вазодилатирующее действие.
In domestic and foreign medical periodical literature, highlighting the problem of ophthalmopathology against the background of coronavirus infection, the lesion of the anterior segment of the eye is most often described. It is extremely hard to find reports about pathology of the retina, optic nerve or central parts of the visual analyzer. However, it is widely acknowledged that there is a high risk of developing coagulopathy against the background of COVID-19 infection, which leads to occlusion and thrombosis of retinal vessels, ischemic neuropathies. The problem of irreversible loss of vision due to circulatory disorders of the retinal vessels was urgent even before the wide spread of coronavirus infection due to the high prevalence of atherosclerosis, hypertension and type 1 and 2 diabetes in the population. Also, it is widely known that occlusions and thrombosis of retinal vessels can be formidable harbingers of the developing life-threatening conditions. Knowledge about the high risk of vascular ophthalmopatology against the background of a previous COVID-19 infection by the primary echelon ophthalmologists, early diagnostics and treatment of ischemic conditions of the posterior segment of the eye will reduce the frequency of irreversible vision loss due to these diseases, secondary neovascular glaucoma cases, and will also help to send patients to the multidisciplinary hospitals in a timely manner for the prevention of fatal complications of coagulopathy. The article provides a brief overview of foreign literary sources regarding the history of outbreaks of coronavirus infection in the world, as well as possible ways of damage to the organ of vision by the coronavirus. A clinical case of damage to the vascular bed of the retina in both eyes due to coagulopathy against the background of pneumonia caused by COVID-19 is presented, which is actual due to the low illumination of similarly cases.
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