Effect of different doses of paricalcitol on the expression of vitamin D receptors in mice liver tissue
Introduction. The high doses of vitamin D lead to undesirable side effects such as hypercalcemia. Paricalcitol (PC) is a biologically active synthetic substance that selectively binds to intracellular vitamin D receptors and does not cause hypercalcemia. The effect of this drug on metabolic pathways...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | Russian |
| Published: |
LLC Center of Pharmaceutical Analytics (LLC «CPHA»)
2023-09-01
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| Series: | Разработка и регистрация лекарственных средств |
| Subjects: | |
| Online Access: | https://www.pharmjournal.ru/jour/article/view/2158 |
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| Summary: | Introduction. The high doses of vitamin D lead to undesirable side effects such as hypercalcemia. Paricalcitol (PC) is a biologically active synthetic substance that selectively binds to intracellular vitamin D receptors and does not cause hypercalcemia. The effect of this drug on metabolic pathways, parathyroid hormone secretion, asthma and liver fibrosis is known, which confirms its wide clinical potential. However, only a few publications have been devoted to the effect of different doses of PC on the state of liver cells, which are the most important site of its metabolism.Aim. To study the effect of intraperitoneal administration of different doses of paricalcitol on the degree of activation of vitamin D receptors and to conduct a morphological assessment of the state of liver tissue in mice.Materials and methods. The experiment involved male BALB/c mice without external pathological signs, weighing 16– 18 g and aged 4–6 weeks, which were divided into 4 groups. Healthy animals of the control group received 100 µl of saline solution intraperitoneally. Animals from the groups 2, 3, and 4 received PC intraperitoneally at the doses of 25 ng/mouse, 50 ng/mouse, and 100 ng/mouse, respectively on the days 1, 2, 4, and 7. Sacrifice was performed on the 10th or 21st day after the onset of the experiment. Histological assessment of liver tissues of animals removed from the experiment on day 10 was performed according to generally accepted histological methods. Immunohistochemical examination was performed automatically in a Bond™- maX immunohistostainer (Leica, Germany). Primary rabbit polyclonal antibodies to the vitamin D receptor were used.Results and discussion. The introduction of PC in different doses consistently increased the total number of liver cells expressing VDR, mainly due to immune cells. An increase in the percentage of intensely stained non-parenchymatous cells (++++ and +++) was observed by the 21st day of the experiment and amounted to 56.0 % in subgroup 2.2, 3.2 – 46.6 % and 4.2 – 48.0 %, in the control group this value was 39.5 %. The liver tissue structure closest to the control was observed in animals that received PC at a dose of 25 ng/mouse. In the groups of mice where the animals received PC at doses of 50 ng/mouse and 100 ng/mouse, certain morphological changes were noted, mainly of a dystrophic and discirculatory nature, which reflected the toxic effect of these doses of PC on the metabolism of hepatocytes.Conclusion. The administration of different doses of PC leads to an increase in VDR expression mainly in non-parenchymatous liver cells that perform immune functions. VDR expression in hepatocytes of all subgroups increased by the 10th day of observation and decreased by the 21st day, which was probably due to the death of these cells. Microscopic examination showed that the use of PC in healthy mice leads to certain dose-dependent changes in the liver, the least toxic dose of PC is 25 ng/mouse. |
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| ISSN: | 2305-2066 2658-5049 |