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Gender differences in the pharmacological actions of pegylated glucagon-Like peptide-1 on endothelial progenitor cells and angiogenic precursor cells in a combination of metabolic disorders and lung emphysema
In clinical practice, the metabolic syndrome (MetS) is often associated with chronic obstructive pulmonary disease (COPD). Although gender differences in MetS are well documented, little is known about sex-specific differences in the pathogenesis of COPD, especially when combined with MetS. Consequently, it is not clear whether the same treatment regime has comparable efficacy in men and women diagnosed with MetS and COPD. In the present study, using sodium glutamate, lipopolysaccharide, and cigarette smoke extract, we simulated lipid metabolism disorders, obesity, hyperglycemia, and pulmonary emphysema (comorbidity) in male and female C57BL/6 mice. We assessed the gender-specific impact of lipid metabolism disorders and pulmonary emphysema on angiogenic precursor cells (endothelial progenitor cells (EPC), pericytes, vascular smooth muscle cells, cells of the lumen of the nascent vessel), as well as the biological effects of pegylated glucagon-like peptide 1 (pegGLP-1) in this experimental paradigm. Simulation of MetS/COPD comorbidity caused an accumulation of EPC (CD45−CD31+CD34+), pericytes, and vascular smooth muscle cells in the lungs of female mice. In contrast, the number of cells involved in the angiogenesis decreased in the lungs of male animals. PegGLP-1 had a positive effect on lipids and area under the curve (AUC), obesity, and prevented the development of pulmonary emphysema. The severity of these effects was stronger in males than in females. Furthermore, PegGLP-1 stimulated regeneration of pulmonary endothelium. At the same time, PegGLP-1 administration caused a mobilization of EPC (CD45−CD31+CD34+) into the bloodstream in females and migration of precursors of angiogenesis and vascular smooth muscle cells to the lungs in male animals. Gender differences in stimulatory action of pegGLP-1 on CD31+ endothelial lung cells in vitro were not observed. Based on these findings, we postulated that the cellular mechanism of in vivo regeneration of lung epithelium was at least partly gender-specific. Thus, we concluded that a pegGLP-1-based treatment regime for metabolic disorder and COPD should be further developed primarily for male patients
Estimation of acute toxicity of a drug based on the complex of lithium citrate, polymethylsiloxane, aluminum oxide
Research Institute of Clinical and Experimental Lymphology has developed an innovative drug based on a complex of lithium citrate, polymethylsiloxane and aluminum oxide (LOAP). Lithium-based drugs are effective in treating bipolar disorders. However, the toxic effects of lithium cause a “narrow therapeutic window”, which limits its clinical use. The creation of the drug LOAP was aimed at creating a prolonged form with a slow release of lithium to reduce toxic properties and use lithium citrate as an active pharmacological agent. At the moment, the lithium complex has no analogues. The purpose of the study was to study the parameters of acute toxicity of the LOAP. Material and methods. When studying acute toxicity, drugs were administered once intragastrically to mice and rats at doses of 12000, 10000, and 5000 mg/kg. Results. A single administration of drugs intragastrically through a probe in the maximum possible doses to mice and rats did not cause the death of animals and did not cause a locally irritating effect on the gastric mucosa. LOAP can be assigned to hazard class 4 (GOST 12.1.007-76)