Effect of liraglutide on microcirculation in rat model with absolute insulin deficiency.

INTRODUCTION: The investigations of angiotropic effects of liraglutide are an issue of significant scientific and practical interest. The successful application of liraglutide has been shown in glycemic control in patients with the type 2 diabetes mellitus (DM), but the effect of liraglutide in patients with type 1 DM has not been completely studied yet in clinical practice. Therefore, the present study is aimed to investigate the effect of liraglutide which is agonist of glucagon-like peptide-1 receptors, on microcirculation in white outbred rats with the alloxan-induced diabetes. MATERIALS AND METHODS: The study was performed with 70 white outbred rats, divided into 4 groups: 1) control group (intact animals (Control)); 2) comparison group (diabetes mellitus (DM)) - animals with the alloxan-induced diabetes; 3) experimental group no. 1 (liraglutide low dose (LLD)) - animals with the alloxan-induced diabetes, which were injected by liraglutide at dosage of 0.2 mg/kg of animal weight per a day; 4) experimental group no. 2 (liraglutide high dose (LHD)) - animals with the alloxan-induced diabetes, which were injected by liraglutide at dosage of 0.4 mg/kg of animal weight per a day. The carbohydrate metabolism disorders, the microcirculation of posterior paw skin, as well as the concentration of catecholamines and markers of endothelial alteration in blood were estimated at the 42nd day of the experiment in the comparison and experimental groups. RESULTS: It was found that the correction of carbohydrate metabolism by liraglutide is succeeded by the normalization of skin perfusion of posterior paw skin of the experimental animals. Recovery of microcirculation is associated with a decrease in vascular tone and stimulation of endothelium-dependent vasodilation, caused by simultaneous decrease of catecholamines, endothelin-1 and asymmetric dimethylarginine (ADMA) concentrations in blood serum. At the same time, the administration of liraglutide on the background of insulin-deficiency results in decrease of endothelial cell alteration markers concentration in blood, such as sE-selectin, syndecan-1, and vascular endothelial growth factor (VEGF). CONCLUSION: Administration of liraglutide leads to the normalization of the carbohydrate metabolism simultaneously with the correction of microcirculation in rats with the absolute insulin deficiency. The demonstrated recovery of microcirculation by liraglutide, which represents an analogue of glucagon-like peptide-1, provides new prospects for its approval as a potential drug for pathogenetic correction of microcirculatory disorders in patients with the type 1 DM.

Influence of the new formulation based on silver alginate microcapsules loaded with tannic acid on the microcirculation of the experimental periodontitis in rats.

The microvascular changes caused by disorders of host immune response to oral microorganisms resulting in long-lasting inflammation of gums play a critical role in the periodontal lesion in the pathogenesis of chronic periodontitis. Current strategies of non-surgical periodontal therapy are aimed at the attainment of anti-inflammatory effects. We hypothesized that the usage of the microencapsulated form of anti-inflammatory substances with vasoactive effects could enhance the efficiency of the therapy by the prolonged release of active components. The prepared suspension of silver-alginate microcapsules loaded with tannic acid in the hydrogel was applied in vivo to the experimental model of periodontitis in rats induced by a ligature. The effect of this formulation was assessed by monitoring changes in local microcirculation performed by the Laser Doppler Flowmetry (1 and 24 h after application of hydrogel on intact gums and 21-days after the start of periodontitis' modeling). Application of the hydrogel containing multicomponent microcapsules to the affected area of gums allows correction of inflammatory microcirculatory disorders in model periodontitis. Immobilization of tannic acid into microcapsules allows increasing the correction of the following parameters: perfusion disorders, neurogenic tone of arterioles, myogenic tone of precapillary sphincters, as well as a venous outflow in the microvasculature of the gums. The hydrogel containing multicomponent microcapsules reduces the vascular inflammatory response in the model of periodontitis. Loading of silver-alginate microcapsules with tannic acid enhances the efficiency of microvascular disorders' correction in the model of periodontitis that suggests the prospects for application of this drug delivery system for non-surgical treatment of periodontitis.

TNF-alpha and gamma-irradiation induced activation of the Salmonella typhimurium reproduction in the organs of infected animals.

The goal of the current work is to determine the role of the TNF-alpha on the activation of the bacterial growth in an in vivo system. In order to reach this goal we studied the dynamics of the reproduction of vegetative forms of Salmonella and the recultivation of non-cultivating forms of Salmonella in infected animals. Experiments have been conducted both on animals that had been injected with exogenous TNF together with bacterial suspension and on animals that had been exposed to gamma-radiation before infection, since it is known that irradiation increases the secretion of TNF. We demonstrate that in all cases the increase in the level of TNF-alpha in animals leads to the activation of the Salmonella growth. Moreover, in this paper we present the data obtained by the method of molecular display on the identification of genes that are highly expressed in the Salmonella cells cultivated in vitro in the presence of TNF.