UDC

616.36-002:615.276-085:544.127:547.854.9:577.164.1

DOI

10.37482/2687-1491-Z074

Authors

Kseniya A. Pazinenko* ORCID: https://orcid.org/0000-0002-3390-4343
Natalʼya N. Chuchkova* ORCID: https://orcid.org/0000-0001-7777-6825
Marina V. Smetanina* ORCID: https://orcid.org/0000-0002-1801-5353

*Izhevsk State Medical Academy (Izhevsk, Udmurt Republic, Russian Federation)

Abstract

The purpose of this paper was to conduct a comparative experimental study of the anti-inflammatory effects of tautomeric forms of orotic acid in the correction of drug-induced hepatitis in rats. Materials and Methods. A total of 40 rats (Rattus norvegicus Berk.) were randomly divided into 5 groups: control group (n = 10); intervention group with drug-induced hepatitis (n = 15); animals with drug-induced hepatitis who were injected with orotic acid (ОА) tautomers: initial oxo-form (n = 5), hydroxy-form (n = 5) and dihydroxyform (n = 5) at a dose of 0.5 g/kg body weight a day in the course of 14 days. The tautomers were obtained by mechanical activation in a planetary ball mill AGO-2C for 1 (hydroxy-form) and 6 (dihydroxyform) hours. In the blood of animals of all experimental groups, the content of leukocytes, granulocytes, lymphocytes, and monocytes was determined. Liver sections were stained with hematoxylin and eosin to assess the histo- and cytostructure of the tissues, and immunohistochemically using a set of monoclonal antibodies to detect the expression of the CD68+ macrophage marker. Results. It was found that when correcting drug-induced hepatitis with the hydroxy-form of OA, the severity of leuko- and monocytosis decreased and the number of lymphocytes was restored. The number of CD68+ macrophages with a pro-inflammatory phenotype decreased in the group receiving the hydroxy-form of OA (by a factor of 1.32; p = 0.019), but remained unchanged at the administration of oxo- and dihydroxy-forms of OA. The intensity of reaction product expression decreased by a factor of 1.5 in the group administered with the initial drug and by a factor of 1.9 in animals administered with mechanically activated drugs (p = 0.0001). Thus, the obtained data indicate a pronounced anti-inflammatory activity of the hydroxyform of OA, which can substantiate its use as a hepatoprotective agent.

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Corresponding author: Natal’ya Chuchkova, address: ul. Kommunarov 281, Izhevsk, 426056, Udmurtskaya Respublika, Russian Federation; e-mail: mig05@inbox.ru
For citation: Pazinenko K.A., Chuchkova N.N., Smetanina M.V. Tautomers of the Orotate Anion Have Anti-Inflammatory Effects in the Correction of Drug-Induced Hepatitis in Rats. Journal of Medical and Biological Research, 2021, vol. 9, no. 4, pp. 366–373. DOI: 10.37482/2687-1491-Z074

Keywords

tautomeric forms of orotic acid, drug-induced hepatitis, blood cells, Kupffer cells, CD68+ liver macrophages, hepatocytes

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