HEMOSTIMULATING PROPERTIES OF THE CONJUGATES OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR WITH ALENDRONIC ACID
The aim of the work is to evaluate the hemostimulating activity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) conjugates with alendronic acid (ALN) in the model of cytostatic myelosuppression and the dynamics of rhGM-CSF accumulation as a part of the conjugate in t...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute
2022-12-01
|
| Series: | Фармация и фармакология (Пятигорск) |
| Subjects: | |
| Online Access: | https://www.pharmpharm.ru/jour/article/view/1198 |
| _version_ | 1797874683103674368 |
|---|---|
| author | G. G. Shimina A. V. Bateneva E. S. Tsyplenkova S. G. Gamaley T. I. Esina E. A. Volosnikova E. D. Danilenko |
| author_facet | G. G. Shimina A. V. Bateneva E. S. Tsyplenkova S. G. Gamaley T. I. Esina E. A. Volosnikova E. D. Danilenko |
| author_sort | G. G. Shimina |
| collection | DOAJ |
| description | The aim of the work is to evaluate the hemostimulating activity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) conjugates with alendronic acid (ALN) in the model of cytostatic myelosuppression and the dynamics of rhGM-CSF accumulation as a part of the conjugate in the bone tissue and bone marrow of mice.Materials and methods. The conjugates obtained by a solid-phase synthesis using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide or periodate oxidation, were used. A hemostimulating activity was evaluated in a model of a cytostatic myelosuppression induced by the administration of cyclophosphamide to CBA/Calac mice. RhGM-CSF preparations were injected subcutaneously for 4-5 days at the dose of 90 µg/kg. After the injections cycle had been completed, the total leukocyte and segmented neutrophil counts were carried out in the blood samples, and the total karyocyte count was carried out in the bone marrow samples.The tissue distribution of rhGM-CSF preparations was assessed in outbred CD-1 mice after a single intravenous administration at the effective dose. The content of rhGM-CSF in blood, femoral tissue and bone marrow was determined by enzyme immunoassay.Results. RhGM-CSF conjugates with ALN have been shown to retain the ability of the original protein to increase the number of leukocytes, segmented blood neutrophils, and bone marrow karyocytes under the action of conjugates. The stimulation of the neutrophil production used to be observed at earlier times than in the case of rhGM-CSF. The increase in the total number of bone marrow cells after the introduction of all three conjugates was more pronounced compared to the original protein (by 34%). The increased hemostimulatory effect of the AEG conjugate was accompanied by a more intense accumulation of rhGM-CSF in the bone tissue and bone marrow of mice. The rhGM-CSF introduced into the conjugate was detected in the bone tissue for 24 h and it circulated in the bloodstream for a longer time compared to the original protein.Conclusion. The data obtained make it possible to conclude that further work on the development of effective hemostimulating drugs based on rhGM-CSF conjugates with ALN, is promising. |
| first_indexed | 2024-04-10T01:35:55Z |
| format | Article |
| id | doaj.art-666d6449a7d74ae783613f5fb3fa7ff5 |
| institution | Directory Open Access Journal |
| issn | 2307-9266 2413-2241 |
| language | Russian |
| last_indexed | 2024-04-10T01:35:55Z |
| publishDate | 2022-12-01 |
| publisher | Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute |
| record_format | Article |
| series | Фармация и фармакология (Пятигорск) |
| spelling | doaj.art-666d6449a7d74ae783613f5fb3fa7ff52023-03-13T09:18:13ZrusVolgograd State Medical University, Pyatigorsk Medical and Pharmaceutical InstituteФармация и фармакология (Пятигорск)2307-92662413-22412022-12-0110547248210.19163/2307-9266-2022-10-5-472-482458HEMOSTIMULATING PROPERTIES OF THE CONJUGATES OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR WITH ALENDRONIC ACIDG. G. Shimina0A. V. Bateneva1E. S. Tsyplenkova2S. G. Gamaley3T. I. Esina4E. A. Volosnikova5E. D. Danilenko6Институт медицинской биотехнологии Федерального бюджетного учреждения науки «Государственный научный центр вирусологии и биотехнологии «Вектор» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаИнститут медицинской биотехнологии Федерального бюджетного учреждения науки «Государственный научный центр вирусологии и биотехнологии «Вектор» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаИнститут медицинской биотехнологии Федерального бюджетного учреждения науки «Государственный научный центр вирусологии и биотехнологии «Вектор» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаИнститут медицинской биотехнологии Федерального бюджетного учреждения науки «Государственный научный центр вирусологии и биотехнологии «Вектор» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаИнститут медицинской биотехнологии Федерального бюджетного учреждения науки «Государственный научный центр вирусологии и биотехнологии «Вектор» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаИнститут медицинской биотехнологии Федерального бюджетного учреждения науки «Государственный научный центр вирусологии и биотехнологии «Вектор» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаИнститут медицинской биотехнологии Федерального бюджетного учреждения науки «Государственный научный центр вирусологии и биотехнологии «Вектор» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаThe aim of the work is to evaluate the hemostimulating activity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) conjugates with alendronic acid (ALN) in the model of cytostatic myelosuppression and the dynamics of rhGM-CSF accumulation as a part of the conjugate in the bone tissue and bone marrow of mice.Materials and methods. The conjugates obtained by a solid-phase synthesis using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide or periodate oxidation, were used. A hemostimulating activity was evaluated in a model of a cytostatic myelosuppression induced by the administration of cyclophosphamide to CBA/Calac mice. RhGM-CSF preparations were injected subcutaneously for 4-5 days at the dose of 90 µg/kg. After the injections cycle had been completed, the total leukocyte and segmented neutrophil counts were carried out in the blood samples, and the total karyocyte count was carried out in the bone marrow samples.The tissue distribution of rhGM-CSF preparations was assessed in outbred CD-1 mice after a single intravenous administration at the effective dose. The content of rhGM-CSF in blood, femoral tissue and bone marrow was determined by enzyme immunoassay.Results. RhGM-CSF conjugates with ALN have been shown to retain the ability of the original protein to increase the number of leukocytes, segmented blood neutrophils, and bone marrow karyocytes under the action of conjugates. The stimulation of the neutrophil production used to be observed at earlier times than in the case of rhGM-CSF. The increase in the total number of bone marrow cells after the introduction of all three conjugates was more pronounced compared to the original protein (by 34%). The increased hemostimulatory effect of the AEG conjugate was accompanied by a more intense accumulation of rhGM-CSF in the bone tissue and bone marrow of mice. The rhGM-CSF introduced into the conjugate was detected in the bone tissue for 24 h and it circulated in the bloodstream for a longer time compared to the original protein.Conclusion. The data obtained make it possible to conclude that further work on the development of effective hemostimulating drugs based on rhGM-CSF conjugates with ALN, is promising.https://www.pharmpharm.ru/jour/article/view/1198рекомбинантный гранулоцитарно-макрофагальный колониестимулирующий фактор человекаалендроновая кислотаконъюгатгемостимулирующая активностьнакопление в костной ткани и костном мозге |
| spellingShingle | G. G. Shimina A. V. Bateneva E. S. Tsyplenkova S. G. Gamaley T. I. Esina E. A. Volosnikova E. D. Danilenko HEMOSTIMULATING PROPERTIES OF THE CONJUGATES OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR WITH ALENDRONIC ACID Фармация и фармакология (Пятигорск) рекомбинантный гранулоцитарно-макрофагальный колониестимулирующий фактор человека алендроновая кислота конъюгат гемостимулирующая активность накопление в костной ткани и костном мозге |
| title | HEMOSTIMULATING PROPERTIES OF THE CONJUGATES OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR WITH ALENDRONIC ACID |
| title_full | HEMOSTIMULATING PROPERTIES OF THE CONJUGATES OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR WITH ALENDRONIC ACID |
| title_fullStr | HEMOSTIMULATING PROPERTIES OF THE CONJUGATES OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR WITH ALENDRONIC ACID |
| title_full_unstemmed | HEMOSTIMULATING PROPERTIES OF THE CONJUGATES OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR WITH ALENDRONIC ACID |
| title_short | HEMOSTIMULATING PROPERTIES OF THE CONJUGATES OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR WITH ALENDRONIC ACID |
| title_sort | hemostimulating properties of the conjugates of granulocyte macrophage colony stimulating factor with alendronic acid |
| topic | рекомбинантный гранулоцитарно-макрофагальный колониестимулирующий фактор человека алендроновая кислота конъюгат гемостимулирующая активность накопление в костной ткани и костном мозге |
| url | https://www.pharmpharm.ru/jour/article/view/1198 |
| work_keys_str_mv | AT ggshimina hemostimulatingpropertiesoftheconjugatesofgranulocytemacrophagecolonystimulatingfactorwithalendronicacid AT avbateneva hemostimulatingpropertiesoftheconjugatesofgranulocytemacrophagecolonystimulatingfactorwithalendronicacid AT estsyplenkova hemostimulatingpropertiesoftheconjugatesofgranulocytemacrophagecolonystimulatingfactorwithalendronicacid AT sggamaley hemostimulatingpropertiesoftheconjugatesofgranulocytemacrophagecolonystimulatingfactorwithalendronicacid AT tiesina hemostimulatingpropertiesoftheconjugatesofgranulocytemacrophagecolonystimulatingfactorwithalendronicacid AT eavolosnikova hemostimulatingpropertiesoftheconjugatesofgranulocytemacrophagecolonystimulatingfactorwithalendronicacid AT eddanilenko hemostimulatingpropertiesoftheconjugatesofgranulocytemacrophagecolonystimulatingfactorwithalendronicacid |