Effects of Dimephosphone on skin survival in conditions of reduced blood circulation

Abstract

Introduction: 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.