Introduction. The drugs affecting a mitochondrial dysfunction, oxidative stresses, apoptosis and inflammation of the vascular wall, have a high potential for the prevention and treatment of atherosclerotic lesions. In this regard, the use of EPOR/CD131 heteroreceptor agonists which have a similar spectrum of pharmacological effects, is one of the promising strategies in the treatment of cardiovascular diseases.Materials and Methods. The study was carried out on 68 C57Bl/6J male mice. Atherosclerosis was simulated in transgenic animals with an endotheliospecific knockdown of the Polg gene by simulating a balloon injury and keeping on a Western diet. Then, the studied drugs were injected once every 3 days at the dose of 20 μg/kg for 27 days. On the 28-th day, the animals were euthanized and the area of atherosclerotic plaques was assessed. The gene expression associated with the processes of inflammation, antioxidant protection, apoptosis, and angiogenesis was also determined in the aortic tissues. In addition, the endothelium protective effect of peptides on primary cultures of endothelial cells of wild and transgenic Polg-D257A mice was studied.Results. No statistically significant effect of drugs on the area of lipid infiltration have been found. However, the studied peptides have significantly reduced the expression of proinflammatory genes (iNos, Icam1, Vcam1, Sele, Il6, Tnfa), the genes associated with angiogenesis (Vegfa, Kdr, and Hif1a), the expression of proapoptic factors; they decreased the Bax/Bcl-2 ratio by more than 1.5 times. In addition, when supplemented with H2 O2 in vitro, peptides dose-dependently increased endothelial cell survival.Conclusion. The erythropoietin-based peptides can be used to improve the functional state of the vascular wall against the background of atherosclerotic lesions and have a depressing effect on pathobiological processes associated with a mitochondrial dysfunction. In addition, the studied peptides have a significant endothelial protective effect in the induction of oxidative stress in vitro.
Introduction:
Nowadays, the group of NSAIDs is used the most widely in order
to treat the inflammatory process. But its long-term administration increases the risk of
complications of pharmacotherapy. Therefore, today it is urgent to search for new molecules
that can selectively block biological targets that directly perceive inflammatory mediators.
One of such targets is TRPA1. ZC02-0012, a compound from the group of substituted
pyrazinopyrimidinones, which is a selective inhibitor of TRPA1 ion channel.
Objective:
The aim of our study was to study the anti-inflammatory activity of an innovative
molecule under the laboratory code ZC02-0012 from the group of selective inhibitors
of TRPA1 ion channel.
Materials and Methods:
Anti-inflammatory activity of ZC02-0012 was studied on the
model of acute exudative inflammation of the paw in response to subplantar injection in
the right hind paw of mice with 0.02 ml of 2% formaldehyde solution. The mass of the
paw was measured after 4 hours (peak edema) after phlogistic injection. The test substance
and the reference drug was administered intragastrically or intramuscularly 45 minutes before
the injection of formaldehyde solution. The presence and intensity of antiinflammatory
activity was judged by the inhibitory effect, represented in percent.
Results and Discussion:
Selective inhibitor of the TRPA1 ion channel ZC02-0012 revealed
the anti-inflammatory activity at doses of 3 and 9 mg/kg, its intensity is comparable to diclofenac
sodium.
Conclusion:
The selective inhibitor of the ion channel TRPA1, a substance under code
ZC02-0012, has an anti-inflammatory activity comparable with diclofenac sodium.
Owing to adoption of the GOELRO plan in 1920 and its stage-by-state implementation, it became possible to meet the country’s needs for intense development of its economy through providing the required amounts of electricity to all sectors of the national economy. Nowadays, the smart grid technologies open the possibility to carry out «digital updating» of the grids to obtain their better observability and controllability, smaller losses in them, and to ensure reliable operation of distributed and renewable power generating facilities, which have become new participants in the electricity market. The use of smart grid technologies opens the possibility to optimally integrate heterogeneous electric power sources, backbone and distribution networks, and also active consumers into a unified electric power complex for achieving the economic and environmental objectives. The article considers modern innovative and prospective technologies of smart grids and outlines historical parallels with the GOELRO plan, which determined the course for electrification of Russia.
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