Impact of new Rexod® injection form on blood microcirculation in rat skin

Abstract

Background. Free radical oxidation underlies many morbid processes in various organs and tissues, including skin. A major antioxidant preventing the free radical impact is superoxide dismutase (SOD). A particularly valued SOD-containing agent is recombinant human SOD, Rexod, possessing a wide spectrum of medical applications in form of lyophilisate. Marketing of a new Rexod® injection preparation in form of solution requires research into its properties, including the impact on blood microcirculation in skin, especially with the lack of relevant clinical trials.Objectives. Evaluation of anticipated positive effects of the new injection form of Rexod® on blood microcirculation in rat skin.Мethods. The new Rexod® preparation impact on blood microcirculation in skin was studied with laser Doppler fl uometry by recording the following non-oscillatory parameters of the basal blood fl ow: microcirculation (MC), mean squared deviation (MSD) and coeffi cient of variation (CV). Blood fl ow fl uctuations were measured in a wavelet analysis at different frequency bands: 0.0095–0.02, 0.02–0.046, 0.07–0.15, 0.15–0.4 and 0.8–0.16 Hz corresponding to endothelial (Ae), neurogenic (An), myogenic (Am), respiratory (Ar) and pulse (Ap) rhythm amplitudes, respectively.Results. The new Rexod® injection preparation at a dose of 8000 U/kg after 15 min of intraperitoneal administration in rats caused a statistically signifi cant (p < 0.05) increase in the blood fl ow fl uctuation amplitudes Ae (43.1%), An (43.4%), Am (60.8%), Ar (58.3%) and Ap (32.0%) compared to the control group. Because the Ae fl uctuations coincide with nitric oxide (NO) emission episodes, such a growth indicates an elevated NO excretion by endothelial cells leading to endothelium-dependent vasodilation. The observed changes in blood microcirculation in skin are also associated with higher integral values of the basal blood fl ow, MC (33.4% increase), MSD (14.0%) and CV (27.6%), although only MC and CV values were statistically signifi cant (p < 0.05). The results obtained suggest that the new injection form of Rexod® stimulates endothelial NO excretion, exerts adrenergic relaxation in smooth muscle cells of arteriolae and arteriovenular anastomoses, reduces precapillary sphincter and arteriolar contractility through Ca2+-dependent muscle relaxation, affects respiratory modulation of the venular blood microcirculatory compartment and vegetative cardiac support, intensifi es arterial blood fl ow by increasing the cardiac output.Conclusion. Application of the new Rexod® injection form improves blood microdynamics in rat skin via stimulating endothelium-dependent and independent vasodilatation and endothelial metabolism, decelerating adrenergic vasomotor activity and peripheral microvascular resistance. These processes in coupling improve blood fl ow to nutritive microvascular bed and normalise venular outfl ow. Our results provide further insights into pharmacodynamics of recombinant human SOD (Rexod).