11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.
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-NAM...
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Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute
2020-01-01
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| Series: | Фармация и фармакология (Пятигорск) |
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| Online Access: | https://www.pharmpharm.ru/jour/article/view/550 |
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| author | M. V. Korokin V. O. Soldatov A. A. Tietze M. V. Golubev A. E. Belykh M. V. Kubekina O. A. Puchenkova T. A. Denisyuk V. V. Gureyev T. G. Pokrovskaya O. S. Gudyrev M. A. Zhuchenko M. A. Zatolokina M. V. Pokrovskiy |
| author_facet | M. V. Korokin V. O. Soldatov A. A. Tietze M. V. Golubev A. E. Belykh M. V. Kubekina O. A. Puchenkova T. A. Denisyuk V. V. Gureyev T. G. Pokrovskaya O. S. Gudyrev M. A. Zhuchenko M. A. Zatolokina M. V. Pokrovskiy |
| author_sort | M. V. Korokin |
| collection | DOAJ |
| description | 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. Theresults 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. |
| format | Article |
| id | doaj-art-fb35357e78b640b7aca9ed89c2cf61da |
| institution | Kabale University |
| issn | 2307-9266 2413-2241 |
| language | Russian |
| publishDate | 2020-01-01 |
| publisher | Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute |
| record_format | Article |
| series | Фармация и фармакология (Пятигорск) |
| spelling | doaj-art-fb35357e78b640b7aca9ed89c2cf61da2025-08-20T03:59:56ZrusVolgograd State Medical University, Pyatigorsk Medical and Pharmaceutical InstituteФармация и фармакология (Пятигорск)2307-92662413-22412020-01-017631232010.19163/2307-9266-2019-7-6-312-32032511-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.M. V. Korokin0V. O. Soldatov1A. A. Tietze2M. V. Golubev3A. E. Belykh4M. V. Kubekina5O. A. Puchenkova6T. A. Denisyuk7V. V. Gureyev8T. G. Pokrovskaya9O. S. Gudyrev10M. A. Zhuchenko11M. A. Zatolokina12M. V. Pokrovskiy13Belgorod State National Research UniversityBelgorod State National Research UniversityUniversity of GothenburgBelgorod State National Research UniversityKursk State Medical UniversityInstitute of Gene Biology of the Russian Academy of SciencesBelgorod State National Research UniversityKursk State Medical UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityScientific Research Centre, Kurchatov InstituteKursk State Medical UniversityBelgorod State National Research UniversityThe 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. Theresults 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.https://www.pharmpharm.ru/jour/article/view/550atherosclerosiserythropoietinratsp-αbcibenitideendothelium |
| spellingShingle | M. V. Korokin V. O. Soldatov A. A. Tietze M. V. Golubev A. E. Belykh M. V. Kubekina O. A. Puchenkova T. A. Denisyuk V. V. Gureyev T. G. Pokrovskaya O. S. Gudyrev M. A. Zhuchenko M. A. Zatolokina M. V. Pokrovskiy 11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats. Фармация и фармакология (Пятигорск) atherosclerosis erythropoietin rats p-αb cibenitide endothelium |
| title | 11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats. |
| title_full | 11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats. |
| title_fullStr | 11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats. |
| title_full_unstemmed | 11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats. |
| title_short | 11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats. |
| title_sort | 11 amino acid peptide imitating the structure of erythropoietin α helix b improves endothelial function but stimulates thrombosis in rats |
| topic | atherosclerosis erythropoietin rats p-αb cibenitide endothelium |
| url | https://www.pharmpharm.ru/jour/article/view/550 |
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