Potentiating interaction of ethoxydol and rosuvastatin in an experimental model of Langendorf-isolated rat heart total ischemia-reperfusion

The study of cardioprotective activity showed that in vitro ethoxydol at a dose of 3.8 × 10-4 g/l can significantly improve the morphofunctional state of cardiomyocytes, which is manifested in an increase in the proportion of postischemic cardiac resumption, reduction of ischemic contracture, and recovery of contractility during the reperfusion perio

Effects of bischofite gel on reparative processes in wound healing

The study showed that the best results were obtained with external use of the gel with bischofite. Actovegin has a less significant but pronounced reparative effect on this model. The least satisfactory results were obtained when applying Contractube

Combination of captopril and darbepoetin alfa attenuate radiation-induced-endothelial dysfunction

The combination of captopril + darbepoetin alfa has a high radio- and endothelioprotective potential and can be recommended for further preclinical and clinical studie

Cytokines in abdominal aortic aneurysm: master regulators with clinical application

Abdominal aortic aneurysm (AAA) is a potentially life-threatening disorder with a mostly asymptomatic course where the abdominal aorta is weakened and bulged. Cytokines play especially important roles (both positive and negative) among the molecular actors of AAA development. All the inflammatory cascades, extracellular matrix degradation and vascular smooth muscle cell apoptosis are driven by cytokine

Retinal abnormalities in transgenic mice overexpressing aberrant human FUS[1-359] gene

The aim of this work was to assess the structural and functional state of the retina in a murine model of ALS caused by overexpression of the aberrant FUS protein [1-359]. The retinal examination was carried out on 12 transgenic and 13 wild-type mice of 2.5-3 months of age. The study revealed not statistically significant higher level of ophthalmoscopic violations in FUS[1-359] mic

Betahistine: targeting on vascular wall aging

Betahistine are routine drug in neurological practice, which is used to correct vertigo. The clinical efficacy of this drug can be caused not only by neuro-, but also by endotheliotropic action. In this review, the main information on the potential mechanisms for the implementation of vasoprotection, including metabolic, NO-ergic, anti-inflammatory and other components of the action are discusse

Investigação do efeito reparador do gel de ectoína em modelo de queima térmica

Due to the ability to create complexes of water molecules on the surface of the mucous membrane, ectoine is a promising compound for the treatment of burns. In male rats (n=30), 2 thermal burns were counteracted under counter-anesthesia, one of which was treated by topical application of the test drugs for 7 days, and the other served as a control. On the 8th day, skin samples in the area of the burn were taken for morphological examination. Histological sections were then scored by independent experts. The best histological picture of thermally damaged tissues was demonstrated by animals receiving ectoine. A less significant, but pronounced reparative effect was observed in histological samples of the actovegin group. The least significant reparative effect was demonstrated by contractubex. Ectoine improved the histological picture, improved repair and reduced the inflammatory response of the tissues and can be recommended for further preclinical studies as a treatment for burns.Debido a la capacidad de crear complejos de moléculas de agua en la superficie de la membrana mucosa, la ectoina es un compuesto prometedor para el tratamiento de las quemaduras. En ratas macho (n = 30), 2 quemaduras térmicas se contrarrestaron con contraestesia, una de las cuales se trató mediante la aplicación tópica de los fármacos de prueba durante 7 días, y la otra sirvió como control. En el octavo día, se tomaron muestras de piel en el área de la quemadura para un examen morfológico. Las secciones histológicas fueron calificadas por expertos independientes. El mejor cuadro histológico de los tejidos dañados térmicamente fue demostrado por los animales que recibieron ectoína. Se observó un efecto reparador menos significativo, pero pronunciado en muestras histológicas del grupo actovegin. El efecto reparador menos significativo fue demostrado por contractubex. Ectoine mejoró el cuadro histológico, mejoró la reparación y redujo la respuesta inflamatoria de los tejidos y puede recomendarse para estudios preclínicos adicionales como tratamiento para las quemaduras.Devido à capacidade de criar complexos de moléculas de água na superfície da membrana mucosa, a ectoína é um composto promissor para o tratamento de queimaduras. Em ratos machos (n = 30), duas queimaduras térmicas foram combatidas sob anestesia, uma das quais foi tratada por aplicação tópica das drogas de teste por 7 dias, e a outra serviu como controle. No oitavo dia, amostras de pele na área da queimadura foram retiradas para exame morfológico. As secções histológicas foram então classificadas por especialistas independentes. O melhor quadro histológico dos tecidos termicamente lesados foi demonstrado pelos animais que receberam ectoína. Um efeito reparador menos significativo, mas pronunciado, foi observado em amostras histológicas do grupo da actovegina. O efeito reparador menos significativo foi demonstrado pelo contratoubex. Ectoine melhorou o quadro histológico, melhorou o reparo e reduziu a resposta inflamatória dos tecidos e pode ser recomendado para estudos pré-clínicos adicionais como tratamento para queimaduras

11-Amino acid peptide imitating the structure of erythropoietin α-helix B improves endothelial function, but stimulates thrombosis in rats

An 11-amino acid peptide imitating the natural structure of B erythropoietin α-helix (P-αB), has a specific affinity to the heterodimeric complex EPOR/CD131. The aim of the study was to test whether P-αB can be positioned as a preventing and treating agent for cardiovascular diseases. Materials and methods. The study was performed on sexually mature male Wistar rats. Endothelial dysfunction was modulated by a 7-days intraperitoneal administration of L-NAME at the dose of 2.5 mg/100 g. P-αB, or erythropoietin (EPO), was used for therapy at the dose of 2.5 µg/100 g × 3 times for 7 days, the total dose was 7.5 µg/100 g. The function of endothelium was estimated by an endothelium-dependent and endothelium-independent vasodilation. In addition, a histological assessment of the abdominal aortic wall state and the analysis of eNos, Tnf and Il-1β genes expression were performed. To estimate prothrombotic properties, P-αB and EPO were administered, at the doses of 2.5 and 5 µg/100 g (3 times a day for 7 days, the total doses were 7.5 µg/100 g and 15 µg/100 g, respectively) and on the 8th day, the time of ferric (III) chloride-induced carotid artery thrombosis was estimated. Results. The results of the functional tests for endothelium-dependent and endothelium-independent vasodilatation, as well as the histological picture of the aorta have evidenced that P-αB and EPO do not affect L-NAME-induced hypertension but improve the endothelium function. At the same time, P-αB shows a significantly higher endothelial-protective activity, reducing the coefficient of endothelial dysfunction from 5.1±0.15 to 2.72±0.12. In addition, P-αB has significantly increased the expression of eNos and reduced the expression level of Tnf and Il-1β mRNA genes. Carrying out Ferric (III) chloride-induced carotid artery thrombosis has revealed that P-αB (5 µg/100 g × 3 times a day for 7 days, total dose was 15 µg/100 g) has a lower but statistically significant prothrombotic activity than EPO. Conclusion. P-αB can be positioned as an atheroprotector because of its ability to prevent the death of endothelial cells, as well as to reduce remodeling and proinflammatory activation of the vascular wall. However, the prothrombotic properties of P-αB limit its use as a preventing and treating agent for atherosclerosis-associated diseases. © 2019 Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute. All rights reserved

STUDY OF ANTIATHEROSCLEROTIC AND ENDOTHELIOPROTECTIVE ACTIVITY OF PEPTIDE AGONISTS OF EPOR/CD131 HETERORECEPTOR

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