No abstract

Preeclampsia is a severe disease of late pregnancy. Etiological factors and a pathogenetic pattern of events still require significant clarification, but it is now recognized that a large role is played by placentation disorders and emerging endothelial dysfunction. The administration of short-chain peptides mimicking the spatial structure of the B erythropoietin chain may become one of the directions of searching for new drugs for preeclampsia prevention and therapy. Simulation of ADMA-like preeclampsia in Wistar rats was performed by the administration of a non-selective NOS blocker L-NAME from the 14th to 20th day of pregnancy. The administration of the pHBSP at the doses of 10 µg/kg and 250 µg/kg corrected the established morphofunctional disorders. The greatest effect was observed at a dose of 250 µg/kg. There was a decrease in systolic and diastolic blood pressure by 31.2 and 32.8%, respectively (p < 0.0001), a decrease in the coefficient of endothelial dysfunction by 48.6% (p = 0.0006), placental microcirculation increased by 82.8% (p < 0.0001), the NOx concentration was increased by 42,6% (p = 0.0003), the greater omentum edema decreased by 11.7% (p = 0.0005) and proteinuria decreased by 76.1% (p < 0.0002). In addition, there was an improvement in the morphological pattern of the fetoplacental complex and the ratio of BAX to Bcl-2 expression which characterizes the apoptotic orientation of the cells.

No abstract

Introduction: The aim of this study was to examine the effectiveness of innovative peptides obtained by addition of polypeptide motifs with antiaggregation activity (Arg-Gly-Asp, Lys-Gly-Asp and Pro-Gly-Pro) to a peptide mimicking the space structure of the α-helix B of erythropoietin pHBSP (Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser). Materials and methods: The cytoprotective activity of innovative peptides mimicking the space structure of the α-helix B of erythropoietin at the doses of 5 μg/ml, 30 μg/ml and 50 μg/ml was studied on human endothelial cell culture in a simulated oxidative stress. An ADMA-like model of preeclampsia was simulated in the experiment. The study was conducted in 260 female Wistar rats, weighing 250–300 g. Results and discussion: Innovative peptides mimicking the space structure of the α-helix B of erythropoietin retain their cytoprotective activity in a simulated oxidative stress in HUVEC cell culture at the doses of 5 μg/ml, 30 μg/ml, and 50 μg/ml. The compounds with laboratory codes P-αB1 and P-αB3 had the most pronounced cytoprotective activity. Administration of N-nitro-L-arginine-methyl ether to pregnant females for 7 days causes the morphofunctional changes similar to clinical changes in preeclampsia. The innovative peptide under laboratory code P-αB4 at the dose of 50 μg/kg mimicking the space structure of the α-helix B of erythropoietin shows the most pronounced protective properties. Conclusion: Innovative peptides mimicking the space structure of the α-helix B of erythropoietin have a pronounced positive influence on the morphofunctional disorders in animals with ADMA-like preeclampsia.

Citation: Lokteva TI, Rozhkov IS, Gureev VV, Gureeva AV , Zatolokina MA, Avdeyeva EV, Zhilinkova LA, Prohoda EE, Yarceva EO (2020) Correction of morphofunctional disorders of the cardiovascular system with asialized erythropoietin and arginase II selective inhibitors KUD 974 and KUD 259 in experimental preeclampsia. Research Results in Pharmacology 6(1): 29-40. https:// Abstract Introduction: Preeclampsia remains one of the most common causes of maternal and perinatal mortality worldwide. A significant role in the pathogenesis of this pathology is assigned to placental ischemia and endothelial dysfunction. Therefore, the aim of the present study was to study the effectiveness of asialized erythropoietin and arginase II selective inhibitors: KUD-259 and KUD-974 in the correction of morphofunctional disorders of the cardiovascular system in experimental preeclampsia. Materials and methods:The study was performed in 260 female Wistar rats, each weighing 250-300 g. An AD-MA-like preeclampsia was reproduced in the experiment. To assess the emerging morphofunctional disorders, the following parameters were used: blood pressure, coefficient of endothelial dysfunction, microcirculation in the placenta, proteinuria, fluid content in the omentum, concentration of terminal metabolites in the blood plasma, and morphometric parameters of fetuses. Results and discussion:The administration of arginase II selective inhibitor KUD-974 in combination with asialized erythropoietin leads to a pronounced correction of emerging changes: a decrease in systolic and diastolic blood pressure in 1.5 and 1.7 times, a decrease in proteinuria in 3.6 times and a decrease in fluid content in the omentum. When arginase II selective inhibitor KUD 974 and asialized erythropoietin are used with methyldopa, the positive effects of the former are enhanced. Conclusion:Arginase II selective inhibitors KUD-259 and KUD-974 and asialized erythropoietin have a pronounced positive effect on the correction of morphofunctional disorders in animals with ADMA-like preeclampsia.