Corvitin effects on bile acids content in the bile of rats with doxycycline induced hypercholesterolemia

A. M. Liashevych, E. M. Reshetnik, V. M. Kolbasynska, S. P. Veselsky, M. Yu. Makarchuk

Abstract


Introduction. Bile acids are specific and important physiologically active metabolic products of cholesterol transformation in hepatocytes. Cholates concentrations in bile reflect the intensity of the biotransformation, synthesis and transport of bile components in the liver tissue. The conversion of cholesterol to bile acids necessary to maintain the sustainability of cholesterol in the blood and prevents the accumulation of cholesterol, triglycerides, toxic metabolites in the liver cells and other organs. So it is important to study effects of various drugs on the metabolism of cholesterol under experimental hypercholesterolemia. Drugs that can normalize the metabolism of cholesterol in the liver and bile acid synthesis from cholesterol in hepatocytes include flavonoids such as quercetin.

Purpose. The aim of our work was to study the Corvitin (water-soluble form of quercetin) action content of bile acids in the bile of rats with experimental doxycycline hypercholesterolemia.

Methods. The studies used animals of three groups: the first – control (intragastric introduction of water during the whole time of the experiment), the second – with experimental hypercholesterolemia (intragastric administration of doxycycline at a dose of 540 mg/kg body weight), the third group – animals with experimental hypercholesterolemia and weekly oral Corvitin at a dose of 1 mg/kg body weight. Bile secretion liver function was studied in acute experiments for all animals groups. Sodium thiopental at a dose of 70 mg/kg was used for anesthesia of animals. In acute experiments, anesthetized rats laparotomy was performed and bile duct cannulated. Then for three hours six samples of bile were collected. Separate fractions of conjugated bile acids (taurocholate, taurochenodeoxycholate and taurodeoxycholate, glycocholate, glycochenodeoxycholate and glycodeoxycholate) and free bile acids (cholate, chenodeoxycholate and deoxycholate) were determined by TLC in samples of bile.

Results. It was found that the taurocholate concentration (content of this bile acid is highest in the bile of rats) decreased at doxycycline hypercholesterolemia and the after Corvitin application. Glycocholate concentration decreased under the doxycycline influence. But after the Corvitin application glycocholate concentration in bile increased and reached baseline. Also Corvitin normalized taurohydroxycholates and glycohydroxycholates bile concentration in rats with doxycycline hypercholesterolemia. There were also identified changes in the content of free (non-conjugated) bile acids in the bile of rats. Cholic acid concentration decreased under the Corvitin and doxycycline influences. But Corvitin significantly increased bile concentration of the free dyhydroxycholates (chenodeoxycholic acids and deoxycholic acids) in doxycycline hypercholesterolemia rats.

Originality. It was firstly shoud that (Corvitin) normalized content of the conjugated bile acids (except taurocholic bile acids) in the male rats bile at doxycycline hypercholesterolemia. Also Corvitin caused decreasing of the cholic acid concentrration and increasing of the chenodeoxycholic and deoxycholic acids concentration in the bile of the rats at doxycycline hypercholesterolemia.

Conclusion. Taurocholic acid concentration decreased both under hypercholesterolemia modeling with the help of the doxycycline and using Corvitin. Corvitin normalized concentrationof the glycocholic acids in rats at doxycycline hypercholesterolemia. Usage of the Corvitin for rats at doxycycline hypercholesterolemia promoted normalization of the tauro- and glyco- dihydroxycholic bile acids concentration. Corvitin caused decreasing of the cholic acid concentration, but it leaded to significant increasing of the free dihydroxycholic bile acids concentration in bile of rats at doxycycline hypercholesterolemia. So, сorvitin can significantly influence the bile acids composition of bile in rats with experimental hypercholesterolemia.


Keywords


liver; bile; bile acids; Corvitin; doxycycline

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