A study of osteoprotective effect of l-arginine, l-norvaline and rosuvastatin on a model of hypoestrogen-induced osteoporosis in rats

Cover Page

Cite item

Abstract

Effect on the microcirculatory bed of the bony tissue is one of promising approaches to treatment of osteoporosis.

Aim. To study anti-osteoporotic properties of endothelioprotectors: L-arginine, L-norvaline and rosuvastatin.

Materials and Methods. Osteoprotective properties of L-arginine, L-norvaline and rosuvastatin, and also of a reference drug– strontium ranelate – were studied on 152 female rats of Wistar line using a model of hypoestrogen-induced osteoporosis. Anti-osteoporotic and endothelioprotective effect of the drugs were evaluated by laser dopplerflowmetry (LDF) of the proximal metaphysis of the femoral bone, morphometry of trabeculae of bone, and also by calculation of the coefficient of endothelial dysfunction.

Results. LDF showed that maximal increase in microcirculation of the proximal metaphysis of the femoral bone, in comparison with animals with untreated osteoporosis (61.52±3.74 perfusion units, PU) was achieved with L-norvaline (115.25±5.36 PU, p<0.001) and rosuvastatin (106.57±5.22 PU, p<0.001), less expressed effect was demonstrated by L-arginine (98.10±4.48 PU, p<0.001) and a reference drug – strontium ranelate (86.49±4.99 PU). A similar tendency was observed in morphometry of trabeculae of bone: in the group with untreated osteoporosis the diameter of trabeculae was 61.68±1.24 µm, in the group with use fL-norvaline – 91.86±1.8 µm (p<0.001), in the group with use of L-arginine – 86.64±1.39 µm (p<0.001) and in the group with use of strontium ranelate – 89.08±1.09 µm.

Conclusion. L-arginine and L-norvaline and also rosuvastatin possess the property of improving a morphofunctional condition of bone tissue and may be recommended for further preclinical study.

About the authors

Oleg S. Gudyrev

Belgorod State National Research University

Author for correspondence.
Email: gudyrev@bsu.edu.ru
ORCID iD: 0000-0003-0097-000X
SPIN-code: 5936-4774
ResearcherId: N-5527-2016

MD, PhD, Associate Professor, Associate Professor of the Department of Pharmacology and Clinical Pharmacology

Russian Federation, Belgorod

Aleksandr V. Faitelson

Kursk State Medical University

Email: gudyrev@bsu.edu.ru
ORCID iD: 0000-0003-3759-6373
SPIN-code: 7389-8181
ResearcherId: A-9809-2017

MD, PhD, Associate Professor, Professor of the Department of Traumatology and Orthopedics

Russian Federation, Kursk

Mikhail S. Sobolev

Kursk State Medical University

Email: gudyrev@bsu.edu.ru
ORCID iD: 0000-0001-7839-2049
SPIN-code: 2987-3470
ResearcherId: A-9473-2019

PhD-Student of the Department of Traumatology and Orthopedics

Russian Federation, Kursk

Mikhail V. Pokrovskiy

Belgorod State National Research University

Email: gudyrev@bsu.edu.ru
ORCID iD: 0000-0002-1493-3376
SPIN-code: 9201-3580
ResearcherId: A-4427-2017

MD, PhD, Professor, Head of the Department of Pharmacology and Clinical Pharmacology

Russian Federation, Belgorod

Tat`yana G. Pokrovskaya

Belgorod State National Research University

Email: gudyrev@bsu.edu.ru
ORCID iD: 0000-0001-6802-5368
SPIN-code: 8338-0100
ResearcherId: A-5281-2017

MD, PhD, Professor, Professor of the Department of Pharmacology and Clinical Pharmacology

Russian Federation, Belgorod

Mikhail V. Korokin

Belgorod State National Research University

Email: gudyrev@bsu.edu.ru
ORCID iD: 0000-0001-5402-0697
SPIN-code: 8385-3508
ResearcherId: A-6652-2017

MD, PhD, Professor, Professor of the Department of Pharmacology and Clinical Pharmacology

Russian Federation, Belgorod

Elena E. Povetka

Belgorod State National Research University

Email: gudyrev@bsu.edu.ru
ORCID iD: 0000-0003-4517-1041
SPIN-code: 3609-4411
ResearcherId: A-8035-2019

Student

Russian Federation, Belgorod

Eduard S. Miller

Belgorod State National Research University

Email: gudyrev@bsu.edu.ru
ORCID iD: 0000-0001-7982-7518
SPIN-code: 8028-5617
ResearcherId: A-7578-2019

Student

Russian Federation, Belgorod

Vladislav O. Soldatov

Belgorod State National Research University

Email: gudyrev@bsu.edu.ru
ORCID iD: 0000-0001-9706-0699
SPIN-code: 8763-8217
ResearcherId: A-7292-2019

Assistant of the Department of Pharmacology and Clinical Pharmacology

Russian Federation, Belgorod

References

  1. Noble le F, Noble le J. Bone biology: Vessels of rejuvenation. Nature. 2014;507(7492):313-4. doi: 10.1038/nature13210
  2. Huang H, Ma L, Kyrkanides S. Effects of vascular endothelial growth factor on osteoblasts and osteoclasts. American Journal of Orthodontics and Dento-facial Orthopedics. 2016;149(3):366-73. doi:10.1016/ j.ajodo.2015.09.021
  3. Prisby RD, Dominguez JM II, Muller-Delp J, et al. Aging and Estrogen Status: A Possible Endothelium-Dependent Vascular Coupling Mechanism in Bone Remodeling. PLoS One. 2012;7(11):e48564. doi: 10.1371/journal.pone.0048564
  4. Xu R, Yallowitz A, Qin A, et al. Targeting skeletal endothelium to ameliorate bone loss. Nature Medicine. 2018;24(6):823-33. doi: 10.1038/s41591-018-0020-z
  5. Rajkumar DSR, Gudyrev OS, Faitelson AV, et al. Study of the influence of L-norvaline, rosuvastatin and their combination on the level of microcirculation in bone tissue in experimental osteoporosis and fractures on its background. Research result: pharmacology and clinical pharmacology. 2016; 2(1):20-4. doi: 10.18413/2313-8971-2016-2-1-20-24
  6. Popolo A, Adesso S, Pinto A, et al. L-Arginine and its metabolites in kidney and cardiovascular disease. Amino Acids. 2014;46(10):2271-86. doi:10.1007/ s00726-014-1825-9
  7. Ivlitskaya IL, Korokin MV, Loktionov AL. Pharmacological efficiency of statins and L-norvalin at an endotoxin-induced endothelial dysfunction. Research result: pharmacology and clinical pharmacology. 2016;2(2):25-35. doi: 10.18413/2313-8971-2016-2-2-25-35
  8. Denisyuk TA, Lazareva GA, Provotorov VYa, et al. Endothelium and cardioprotective effects of HMG-Co-A-Reductase in combination with L-arginine in endothelial dysfunction modeling. Research Result: Pharmacology and Clinical Pharmacology. 2016;2(1):4-8. doi: 10.18413/2313-8971-2016-2-1-4-8
  9. Cho KJ, Hill MM, Chigurupati S, et al. Therapeutic levels of the hydroxmethylglutaryl-coenzyme A reductase inhibitor lovastatin activate Ras signaling via phospholipase D2. Molecular and Cellular Biology. 2011;31(6):1110-20. doi: 10.1128/MCB.00989-10
  10. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990;343(6257):425-30. doi: 10.1038/343425a0
  11. Van Aelst L, D’Souza-Schorey C. Rho GTPases and signaling networks. Genes & Development. 1997;11(18):2295-322. doi: 10.1101/gad.11.18.2295
  12. Laufs U, Liao JK. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. Journal of Biological Chemistry. 1998;273(37):24266-71. doi: 10.1074/jbc.273.37.24266
  13. Laufs U, La Fata V, Plutzky J, et al. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation.1998;97(12):1129-35. doi: 10.1161/01.cir.97.12.1129
  14. Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circulation Research. 2017;120(1):229-43. doi: 10.1161/CIR-CRESAHA.116.308537
  15. Steyers CM III, Miller FJ. Endothelial dysfunction in chronic inflammatory diseases. International Journal of Molecular Sciences. 2014;15(7):11324-49. doi: 10.3390/ijms150711324

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Results of the influence of L-arginine, L-norvaline, rosuvastatin and strontium renelate on the blood supply of the proximal metaphysis of femoral bone in 8 weeks after bilateral ovariectomy

Download (73KB)
3. Fig. 2. Results of influence of L-arginine, L-norvaline, rosuvastatin and strontium renelate on the average width of trabeculae of proximal metaphysis of femoral bone in 8 weeks after bilateral ovariectomy

Download (73KB)

Copyright (c) 2019 Gudyrev O.S., Faitelson A.V., Sobolev M.S., Pokrovskiy M.V., Pokrovskaya T.G., Korokin M.V., Povetka E.E., Miller E.S., Soldatov V.O.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies