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Osochuk S.S., Yakovleva O.S., Martsinkevich A.F.
The influence of atorvastatin and alpha-calcidol joint application on the content of 1.25 dihydroxycholecalciferol and protein PSSK9 in the laboratory rats blood
Vitebsk State Order of Peoples’ Friendship Medical University, Vitebsk, Republic of Belarus

Vestnik VGMU. 2019;18(6):23-29.

Previously, we have found that the combined use of atorvastatin and α-calcidol  during 90 days increases the cholesterol content of low density lipoproteins (LDL-C) and has a higher mineralizing activity compared to atorvastatin monotherapy. It is known that one of the mechanisms for increasing LDL cholesterol under the influence of statins is their ability to stimulate the production of proprotein convertase subtilisin / kexin 9 (PCSK9), which eliminates low-density lipoprotein receptors from the cell surface. In connection with the above the goal of the present work was to establish the possibility of a connection between the increase in LDL cholesterol and the increase in PCSK9 as well as the potentiation of the mineralizing activity of α-calcidol by the possibility of its steric interaction with the active center of CYP2R1 (25-hydroxylase).
To achieve this goal, a study was conducted on 120 non-inbred laboratory male rats, divided into 4 groups: intact, placebo (intragastric administration of 1% starch), intragastric administration of atorvastatin (10 mg/kg) on 1% starch, and the combined administration of atorvastatin and α-calcidol (0.1 mcg/kg). In their blood, the content of PCSK9 and 1.25(OH)2D3 was determined by enzyme immunoassay. The peculiarities of steric interactions of α-calcidol and the active center of CYP2R1 (25-hydroxylase) were studied in AutoDock VINA and LigandScout programs.
It has been found that the increase in the low-density lipoprotein cholesterol is due to an increase in PCSK9, and α-calcidol is able to act as a steric inhibitor of CYP2R1. The assumption has been made about the impossibility of linking the activity of α-calcidol potentiating bone tissue calcification with its conversion to 1.25(OH)2D3. Perhaps the mineralizing activity is associated with the ability of α-calcidol to convert to 1.20(OH)2D3, which has the activity similar to 1.25(OH)2D3.
Key words: rats, vitamin D, PCSK9 protein, atorvastatin, α-calcidol.

The research was conducted within the frames of Scientific Investigations State Programme «Fundamental and Applied Sciences to Medicine».


1. Yakushevskaya OV. Active vitamin D metabolites in the treatment of postmenopausal osteoporosis. Med Sovet. 2017;(2):100-4. (In Russ.)
2. Buyanova SV, Osochuk SS. The effect of statins on the hormonal spectrum of blood and cholesterol in the adrenal glands of white laboratory rats. Vestn VGMU. 2014;13(1):31-7. (In Russ.)
3. Osochuk SS, Yakovleva OS. The effect of atorvastatin and α-calcidol on the mineral composition of tooth bone tissue in the experiment. Laborator Diagnostika Vostoch Evropa. 2018;7(2):250-7. (In Russ.)
4. Osochuk SS, Yakovleva OS. The effect of long-term administration of atorvastatin and 1-cholecalciferol on the composition of native rat lipoprotein complexes. Laborator Diagnostika Vostoch Evropa. 2017;6(4):465-70. (In Russ.)
5. Casanovas A, Parramon N, de la Cruz F, Andrés O, Terencio J, López-Tejero MD, et al. Retroperitoneal white adipose tissue lipoprotein lipase activity is rapidly down-regulated in response to acute stress. J Lipid Res. 2007 Apr;48(4):863-8. doi:
6. Benimetskaya KS, Atyukov PA, Astrakov SV, Ragino YuI. New possibilities of lipid-lowering therapy. Sibir Med Obozrenie. 2017;(4):65-81. (In Russ.)
7. Dolci GS, Portela LV, Onofre de Souza D, Medeiros Fossati AC. Atorvastatin-induced osteoclast inhibition reduces orthodontic relapse. Am J Orthod Dentofacial Orthop. 2017 Mar;151(3):528-538. doi:
8. Browne RW, Weinstock-Guttman B, Zivadinov R, Horakova D, Bodziak ML, Tamaño-Blanco M5, et al. Serum lipoprotein composition and vitamin D metabolite levels in clinically isolated syndromes: Results from a multi-center study. J Steroid Biochem Mol Biol. 2014 Sep;143:424-33. doi:
9. Nimptsch K, Platz EA, Willett WC, Giovannucci E. Association between plasma 25-OH vitamin D and testosterone levels in men. Clin Endocrinol (Oxf). 2012 Jul;77(1):106-12. doi:
10. Hagenfeldt Y, Eriksson H, Björkhem I. Stimulatory effect of testosterone on renal 25-hydroxyvitamin D3-1α-hydroxylase in guinea pig. Biochim Biophys Acta. 1989 Mar;1002(1):84-8. doi:
11. Holick MF. Resurrection of vitamin D defciency and rickets. J Clin Invest. 2006 Aug;116(8):2062-72. doi:
12. AutoDock Vina – molecular docking. Available from: [Accessed 28th Nov 2019].
13. Ligand Scout – User friendly advanced molecular design. Available from:
14. RCSB Protein Data Bank. Available from: [Accessed 28th Nov 2019].
15. The R Project for Statistical Computing. Available from: [Accessed 28th Nov 2019].
16. Borovikov VP. STATISTICA. The art of computer data analysis. 2-e izd. Saint Petersburg, RF: Piter; 2003. 688 р. (In Russ.)
17. Tuckey RC, Janjetovic Z, Li W, Nguyen MN, Zmijewski MA, Zjawiony J, et al. Metabolism of 1α-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1α,20-dihydroxyvitamin D3. J Steroid Biochem Mol Biol. 2008 Dec;112(4-5):213-9. doi:

Information about authors:
Osochuk S.S. – Doctor of Medical Sciences, professor, head of the Scientific-Research Laboratory, Vitebsk State Order of Peoples’ Friendship Medical University;
Yakovleva O.S. – Master of Medical Sciences, senior lecturer of the Chair of Pediatric Dentistry & Orthodontics with the course of the Faculty for Advanced Training & Retraining, Vitebsk State Order of Peoples’ Friendship Medical University;
Martsinkevich A.F. – Candidate of Biological Sciences, senior lecturer of the Chair of General & Clinical Biochemistry with the course of the Faculty for Advanced Training & Retraining, Vitebsk State Order of Peoples’ Friendship Medical University.

Correspondence address: Republic of Belarus, 210009, Vitebsk, 27/3 Frunze ave., Vitebsk State Order of Peoples’ Friendship Medical University, Scientific-Research Laboratory. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Sergey S. Osochuk.

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