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».
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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.