Abstract
The aim of the study was to analyze the microvasculation of the liver in administration of tautomeric forms of orotic acid for a methionine-induced liver pathology to assess the efficacy of the modified drugs and the potentialof their clinical use.Material and methods. The study included 30 white outbred rats, that were simulated methionine induced hyperhomocysteinemia by the administration of methionine, dosage 0.15 g/100 g of the body we ight, via food during 4 weeks. Animals with hyperhomocysteinemia were divided into 4 groups: animals of group 1 received orotic acid (OA) in the initial form (oxo-tautomer), animals of group 2 received hydroxy–tautomer OA after mechanomodification for 1 hour, animals of group 3 received dihydroxy-tautomer OA after mechanomodification for 6 hours. Histological preparations of the liver were used to evaluate the area of hepatocytes; diameters and areas of the central vein, the interlobular vein and artery, the bile duct, and the Visotto coefficient were calculated.Results. Morphometric data of the hepatic microvascular bloodstream with simulated hyperhomocysteinemia evidenced a general increase in the diameter and area of blood vessels, changes affected the system of blood inflow and outflow at the organ level. Administration of OA had a normalizing effect on the liver bloodflow, but the effects were different: the most pronounced effect was detected in administration of the hydroxy-form of the preparation, this can be explained by a modificationin the dispersion of the preparation (without changing the crystal lattice), an increase in the rate of dissolution in water and aqueous solutions, an increasein the number of functionally active groups in the heterocycle of the hydroxy-form of OA. Thus, the hydroxy-tautomer of orotic acid had the greatest efficacy relating to vasodilation of microvessels of the liver bloodstream in hyperhomocysteinemia; the fact suggesting feasibility of its further study in the clinical environment.
Highlights
Цель исследования – провести анализ микрососудистого русла печени при введении таутомерных форм оротовой кислоты на фоне метионин-индуцированной патологии печени для оценки эффективности применения модифицированных препаратов и возможности их клинического использования
Animals with hyperhomocysteinemia were divided into 4 groups: animals of group 1 received orotic acid (OA) in the initial form, animals of group 2 received hydroxy–tautomer OA after mechanomodification for 1 hour, animals of group 3 received dihydroxy-tautomer OA after mechanomodification for 6 hours
Histological preparations of the liver were used to evaluate the area of hepatocytes; diameters and areas of the central vein, the interlobular vein and artery, the bile duct, and the Visotto coefficient were calculated
Summary
Цель исследования – провести анализ микрососудистого русла печени при введении таутомерных форм оротовой кислоты на фоне метионин-индуцированной патологии печени для оценки эффективности применения модифицированных препаратов и возможности их клинического использования. Морфометрические данные анализа микрососудистого кровеносного русла печени при метионин-обусловленной гипергомоцистеинемии свидетельствуют об общем увеличении диаметра и площади, изменения затрагивают как системы притока, так и оттока крови на органном уровне. Наибольшую эффективность в отношении гипергомоцистеинемической вазодилятации микрососудов кровеносного русла печени проявляет гидрокситаутомер оротовой кислоты, что предполагает целесообразность дальнейшего ее изучения в условиях клинической апробации. The aim of the study was to analyze the microvasculation of the liver in administration of tautomeric forms of orotic acid for a methionine-induced liver pathology to assess the efficacy of the modified drugs and the potential of their clinical use
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