Ukr.Biochem.J. 2017; Volume 89, Issue 5, Sep-Oct, pp. 106-116
doi: https://doi.org/10.15407/ubj89.05.106
The features of bile acids exchange in rats under the influence of corvitin
T. V. Vovkun1, P. I. Yanchuk1, L. Ya. Shtanova1, S. P. Veselskiy1,
N. B. Filimonova1, A. S. Shalamay2, V. G. Vedmid2
1ERC “Institute of Biology and Мedicine”, National Taras Shevchenko
University of Kyiv, Ukraine;
2PJSC SIC “Borshchahivskiy Chemical Pharmaceutical Plant”, Kyiv, Ukraine;
e-mail: shtanova@ukr.net
Corvitin is a soluble form of quercetin (QUE) and its effects are based on the ability to inhibit the activity of 5-lipoxygenase and to block the formation of leukotrienes. Corvitin increases bloodflow in the stomach, pancreas and liver, but its influence on the excretory liver function has not been studied. We investigated the effect of corvitin (2.5, 5, 10 mg/kg intraportally) on bile formation, determined the biliary content of total, free and conjugated bile acids (BAs). Free and conjugated BAs were separated by thin layer chromatography method. It was shown that corvitin increased the content of total BAs in the bile of rats in all tested groups. At a dose of 2.5 mg/kg flavonoid did not сhange free BAs secretion, but while elevated the content of conjugated BAs. Both free and conjugated BAs secretion was increased in rats treated with corvitin at a dose of 5 mg/kg. Increasing of corvitin dose to 10 mg/kg resulted in enhanced secretion of free BAs. Consequently, inhibition of leukotrienes synthesis by corvitin is followed by modulation of total, free and conjugated BAs formation and secretion into the bile.
Keywords: 5-lipoxigenase, bile secretion, conjugated BAs, corvitin, free BAs, leukotrienes, total BAs
References:
- Werz O. 5-lipoxygenase: cellular biology and molecular pharmacology. Curr Drug Targets Inflamm Allergy. 2002 Mar;1(1):23-44. PubMed, CrossRef
- Beckh K, Lange AB, Adler G, Weidenbach H.Effects of nitric oxide on leukotriene D4 decreased bile secretion in the perfused rat liver. Life Sci. 1997;61(19):1947-52. PubMed, CrossRef
- Cincu RN, Rodríguez-Ortigosa CM, Vesperinas I, Quiroga J, Prieto J. S-adenosyl-L-methionine protects the liver against the cholestatic, cytotoxic, and vasoactive effects of leukotriene D4: a study with isolated and perfused rat liver. Hepatology. 1997 Aug;26(2):330-5. PubMed, CrossRef
- Boughton-Smith NK, Whittle BJ. Failure of the inhibition of rat gastric mucosal 5-lipoxygenase by novel acetohydroxamic acids to prevent ethanol-induced damage. Br J Pharmacol. 1988 Sep;95(1):155-62. PubMed, PubMedCentral, CrossRef
- Li T, Francl JM, Boehme S, Chiang JY. Regulation of cholesterol and bile acid homeostasis by the cholesterol 7α-hydroxylase/steroid response element-binding protein 2/microRNA-33a axis in mice. Hepatology. 2013 Sep;58(3):1111-21. PubMed, PubMedCentral, CrossRef
- Monte MJ, Marin JJ, Antelo A, Vazquez-Tato J. Bile acids: chemistry, physiology, and pathophysiology. World J Gastroenterol. 2009 Feb 21;15(7):804-16. PubMed, PubMedCentral, CrossRef
- Lin SY, Wang YY, Chen WY, Chuang YH, Pan PH, Chen CJ. Beneficial effect of quercetin on cholestatic liver injury. J Nutr Biochem. 2014 Nov;25(11):1183-1195. PubMed, CrossRef
- Choi EJ, Chee KM, Lee BH. Anti- and prooxidant effects of chronic quercetin administration in rats. Eur J Pharmacol. 2003 Dec 15;482(1-3):281-5. PubMed, CrossRef
- Parkhomenko AN, Kozhukhov SN, Moybenko AA, Gavrilenko TI. 5-lipoxygenase blocker Corvitin: effect on markers of inflammation and endothelial dysfunction in patients with acute myocardial infarction. Rational Pharmacotherap. 2008;2(1):27-35.
- Vovkun TV, Yanchuk PI, Shtanova LY, Veselskу SP, Baranowskyy VA. Effect of corvitin on secretory processes and blood flow in the rat gastric mucosa. Int J Physiol Pathophysiol. 2013;4(4):335-343. CrossRef
- Vovkun TV, Yanchuk PI, Shtanova LY, Veselsyy SP, Baranovskyy VA. Changes in gastric function in rats after intragastric introduction of corvitin at high doses. Fiziol Zh. 2014;60(3):38-45. (In Ukrainian). PubMed
- Vovkun TV, Yanchuk PI, Shtanova LY, Shalamay AS. Tissue blood flow in the digestive organs of rats with acute pancreatitis after corvitin administration. Fiziol Zh. 2015; 61(6): 53-59. PubMed, CrossRef
- Ghazaee SP, Gorenko ZA, Karbovska LS, Veselsky SP, Yanchuk PI, Makarchuk MY. Desmopressin stimulates bile secretion in anesthetized rats. Gen Physiol Biophys. 2010 Jun;29(2):151-9. PubMed, CrossRef
- Tang Y, Gao C, Xing M, Li Y, Zhu L, Wang D, Yang X, Liu L, Yao P. Quercetin prevents ethanol-induced dyslipidemia and mitochondrial oxidative damage. Food Chem Toxicol. 2012 May;50(5):1194-200. PubMed, CrossRef
- Ofem OE, Ikpi DE, Essien NM. Increased bile flow rate and altered composition of bile induced by ethanolic leaf extract of Azadirachta indica (neem) in rats. Nig J Exp Clin Biosci. 2013; 1(1): 18-22. CrossRef
- Vovkun TV, Yanchuk PI, Shtanova LY, Veselskyy SP, Shalamay AS. Exocrine function of the liver in rats with exposure corvitin. Fiziol Zh. 2016; 62(3): 30-38. CrossRef
- Zhang M, Xie Z, Gao W, Pu L, Wei J, Guo C. Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats. Nutr Res. 2016 Mar;36(3):271-9. PubMed, CrossRef
- Chavez-Santoscoy RA, Gutierrez-Uribe JA, Granados O, Torre-Villalvazo I, Serna-Saldivar SO, Torres N, Palacios-González B, Tovar AR. Flavonoids and saponins extracted from black bean (Phaseolus vulgaris L.) seed coats modulate lipid metabolism and biliary cholesterol secretion in C57BL/6 mice. Br J Nutr. 2014 Sep 28;112(6):886-99. PubMed, CrossRef
- Strange RC. Hepatic bile flow. Physiol Rev. 1984 Oct;64(4):1055-102. PubMed
- Keppler D. Progress in the Molecular Characterization of Hepatobiliary Transporters. Dig Dis. 2017;35(3):197-202. PubMed, CrossRef
- Padma VV, Lalitha G, Shirony NP, Baskaran R. Effect of quercetin against lindane induced alterations in the serum and hepatic tissue lipids in wistar rats. Asian Pac J Trop Biomed. 2012 Nov;2(11):910-5. PubMed, PubMedCentral, CrossRef
- Root C, Smith CD, Sundseth SS, Pink HM, Wilson JG, Lewis MC. Ileal bile acid transporter inhibition, CYP7A1 induction, and antilipemic action of 264W94. J Lipid Res. 2002 Aug;43(8):1320-30. PubMed
- Kakiyama G, Iida T, Yoshimoto A, Goto T, Mano N, Goto J, Nambara T, Hagey LR, Hofmann AF. Chemical synthesis of (22E)-3 alpha,6 beta,7 beta-trihydroxy-5 beta-chol-22-en-24-oic acid and its taurine and glycine conjugates: a major bile acid in the rat. J Lipid Res. 2004 Mar;45(3):567-73. PubMed, CrossRef
- Small DM, Rapo S. Source of abnormal bile in patients with cholesterol gallstones. N Engl J Med. 1970 Jul 9;283(2):53-7. PubMed, CrossRef
- Gu JJ, Hofmann AF, Ton-Nu HT, Schteingart CD, Mysels KJ. Solubility of calcium salts of unconjugated and conjugated natural bile acids. J Lipid Res. 1992 May;33(5):635-46. PubMed
- Ikeda S, Tachikawa M, Akanuma S, Fujinawa J, Hosoya K. Involvement of γ-aminobutyric acid transporter 2 in the hepatic uptake of taurine in rats. Am J Physiol Gastrointest Liver Physiol. 2012 Aug 1;303(3):G291-7. PubMed, CrossRef
- Cohen DE. Hepatocellular transport and secretion of biliary lipids. Curr Opin Lipidol. 1999 Aug;10(4):295-302. PubMed, CrossRef
- El-Desoky AE, Delpy DT, Davidson BR, Seifalian AM. Assessment of hepatic ischaemia reperfusion injury by measuring intracellular tissue oxygenation using near infrared spectroscopy. Liver. 2001 Feb;21(1):37-44. PubMed, CrossRef
- Fiorani M, Guidarelli A, Blasa M, Azzolini C, Candiracci M, Piatti E, Cantoni O. Mitochondria accumulate large amounts of quercetin: prevention of mitochondrial damage and release upon oxidation of the extramitochondrial fraction of the flavonoid. J Nutr Biochem. 2010 May;21(5):397-404. PubMed, CrossRef
- Davis JM, Murphy EA, Carmichael MD, Davis B. Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1071-7. PubMed, CrossRef
- Carrasco-Pozo C, Tan KN, Reyes-Farias M, De La Jara N, Ngo ST, Garcia-Diaz DF, Llanos P, Cires MJ, Borges K. The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic β-cells, glycemic control and inflammation: In vitro and in vivo studies. Redox Biol. 2016 Oct;9:229-243. PubMed, PubMedCentral, CrossRef
