Part II

The molecular mechanisms of the pharmacological action of SS-68 were chosen as the focus for this study. From the point of view of molecular pharmacology, SS-68 can be attributed to an antiarrhythmic drug with a mixed type of actio

Benzofurocaine: effects on experimental periodontitis, anti-diabetic activity and molecular mechanisms of action

Introduction: A promising compound for the treatment of inflammatory periodontal diseases is benzofuracaine (BFC). BFC has pronounced anti-inflammatory, analgesic, reparative, hypoglycemic and other effects. Objective: To assess the influence of benzofuracaine on experimental periodontitis and to study its antidiabetic activity and molecular mechanisms of action Materials and methods: The work was performed on 232 white nonlinear rats of both sexes and 55 male mice. To assess the effect of BFС on experimental periodontitis, the amount of gingival fluid (AGF) was determined, an in-depth morphofunctional study of periodontal tissues was conducted, as well as the study of the biochemical composition of the gingiva and blood. Antidiabetic properties were studied using the glucose tolerance test (GTT), as well as the assessment of endothelium-dependent vasodilation and transmembrane K+-currents on an isolated aortic segment of rats with streptozotocin-induced diabetes mellitus (DM). Results and discussion: In experimental periodontitis, BFC improves the morphological picture and decreases AGF, increases the level of blood microcirculation in the attached gingiva, has a normalizing effect on the prekallikrein-kallikrein system, reduces the synthesis of bradykinin, proinflammatory cytokines and PGE2, increases the level of VEGF, reduces the level of endothelin-1, increases the ATP content and NADH-ubiquinone-reductase activity, exhibits antioxidant properties, reduces the content of nitrosothiols and NO metabolites (NO2/NO3), increases the level of transferrin; when conducting a glucose tolerance test in mice, it reduces the level of glucose in the blood, but in this respect is inferior to glibenclamide, has a hypoglycemic effect in the early stages of diabetes (30 days), tends to restore endothelium-dependent dilatation of smooth muscle cells (SMC) of the aorta and does not affect the functioning of the K+-channels of the aortic SMC. Conclusion: BFС is an effective drug for the treatment of periodontitis and can be recommended for further preclinical and clinical studies

Mafusol and its combination with REXOD as correctors of reduced blood circulation in the skin associated with normoglycemia or diabetes mellitus complicated by exogenous hypercholesterolemia

Introduction: The search for and development of new highly active medications and their combinations of the appropriate direction of action remains an urgent problem due to the complications of diabetes mellitus, especially burdened with atherosclerosis, including skin and vascular lesions. Materials and methods: The acute toxicity, histoprotective and dermatoprotective effects of mafusol, rexod, alprostadil and their combinations were studied in male rats with normoglycemia and alloxan diabetes complicated by exogenous hypercholesterolemia. Results: The combination of mafusol with rexod is less toxic than mafusol. In arteriovenous insufficiency of the tail, ischemia of the skin fold and skin flap, mafusol (6.25, 12.5 and 25.0 mg/kg in terms of fumarate), rexod (0.01 and 0.02 mg/kg) and especially their combination (6.25 and 0.01 mg/kg) have significant histoprotective, dermatoprotective, hypoglycemic and lipid-lowering effects, both in normoglycemia and alloxan diabetes complicated by exogenous hypercholesterolemia. Alprostadil (10 mg/kg) and especially its combination with mafusol (6.25 mg/kg) have a dermatoprotective effect. Discussion: Rexod reduces the acute toxicity of mafusol. The dermatoprotective effect of mafusol, rexod and, to a greater extent, their combination may be associated with increased microhemocirculation, antihypoxic properties and activation of energy processes in the skin, normalization of carbohydrate and lipid metabolism in alloxan diabetes, complicated by exogenous hypercholesterolemia, increased reserve capacity of the antioxidant system, and possibly with the ability of mafusol and rexod to reduce blood viscosity and improve rheological properties of the blood. The combination of mafusol with alprostadil increases the dermatoprotective activity of the latter. Conclusion: Combinations of mafusol with rexod and alprostadil can be recommended for clinical study as dermatoprotective agents for treating traumatic injuries and diabetes mellitus complicated by atherosclerosis