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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2017; 63(5): 21-27


I.S. Chernuha1, Ye.M. Reshetnik1, S.P. Veselsky1, A.G. Reznikov2, M.Yu. Makarchuk1

  1. Kyiv National Taras Shevchenko University, Kyiv, Ukraine
  2. V.P. Komisarenko Institute of Endocrinology and Metabolism Academy of Medical Sciences of Ukraine, Kyiv, Ukraine


The effects of flutamide (25 mg / kg, intragastric, daily, for three days) on bile formation in male rats were investigated. The volume rate of bile secretion decreased in male rats under the influence of flutamide. It was found a significant reduction of the glycoconjugated bile acids concentration in the bile of the male rats under flutamide action. So, glycochenodeoxycholate and glycodeoxycholate concentration in the bile are significantly lower (16,3 – 34,5 %) in male rats under the flutamide action than in bile samples of the control group animals. But it was found that flutamide does not change the ratio of the total conjugated bile acids to unconjugated bile acids. Flutamide inhibits hydroxylation of bile acids in the male rats. The coefficient of the bile acids hydroxylate is decreased under the influence of flutamide compared to control by 10,1%. Thus, flutamide decreases bile flow, conjugation of the bile acids with glycine and glycoconjugates transport into the bile.

Keywords: liver; bile; bile acid; androgen receptors; flutamide


    Klimyuk OV, Bonzik OV, Reshetnik EM, Veselsky SP, Makarchuk MYu. Peculiarities of bile formation in rats of different sex in estron influence. Fiziol Zh. 2011;57(6): 52-8. [Ukrainian].   Reznikov AG Reproductive endocrinology: from basic research to clinical medicine. Health Ukr Reproductol. 2012;2:16-7. [Russian].   Glaser S, DeMorrow S, Francis H, Ueno Y, Gaudio E, Vaculin S, Venter J, Franchitto A, Onori P, Vaculin B, Marzioni M,Wise C, Pilanthananond M, Savage J, Pierce L, Mancinelli R, Alpini G. Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms. J Physiol Gastro Liver Physiol. 2008;295(1):124-36. CrossRef PubMed PubMedCentral   Reznikov OG, Chaikovska LV, Polyakova LI, Sachynska OV, Yanishevsky OV. Age-related peculiarities of the response of male rat reproductive system to letrozole. J Endocrin. 2015;20(1):425-30. [Ukrainian].   Mancinelli R, Onori P, Gaudio E, DeMorrow S, Franchitto A, Francis H, Glaser S, Carpino G, Venter J, Alvaro D, Kopriva S, White M, Kossie A, Savage J, Alpini G. Follicle-stimulating hormone increases cholangiocyte proliferation by an autocrine mechanism via cAMP-dependent phosphorylation of ERK1/2 and Elk-1. J Physiol Gastro Liver Physiol. 2009;297(1):11-6. CrossRef PubMed PubMedCentral   Kapshuk IM. Features of treatment of polycystic ovary syndrome on the overweight background. Reprod Endocrin. 2015;5(25):21-6. [Ukrainian]. CrossRef   Hinchliffe SA, Woods S, Gray S, Burt AD. Cellular distribution of androgen receptors in the liver. J Clin Pathol. 1996;49(5):418-20. CrossRef PubMed PubMedCentral   Gao X, Xie C, Wang Y, Luo Y, Yagai T, Sun D, Qin X, Krausz KW, Gonzalez FJ. The antiandrogen flutamide is a novel aryl hydrocarbon receptor ligand that disrupts bile acid homeostasis in mice through induction of Abcc4. Biochem. Pharmacol. 2016;1(119):93-104. CrossRef PubMed PubMedCentral   Ma WL, Hsu CL, Wu MH, Wu CT, Wu CC, Lai JJ, Jou YS, Chen CW, Yeh S, Chang C. Androgen receptor is a new potential therapeutic target for the treatment of hepatocellular carcinoma. J Gastroenter. 2008;135(3):947-55. CrossRef PubMed PubMedCentral       Yang F, Priester S, Onori P, Venter J, Renzi A, Franchitto A, Munshi MK, Wise C, Dostal DE, Marzioni M, Saccomanno S, Ueno Y, Gaudio E, Glaser S. Castration inhibits biliary proliferation induced by bile duct obstruction: novel role for the autocrine trophic effect of testosterone. J Physiol Gastro Liver Physiol. 2011;301(6):981-91. CrossRef PubMed PubMedCentral   Filimonova NB, Fil IO, Mikhailova TS. Statistical analysis of data pursuant to the science-based medicine. Initial analysis of quantitative data, experimental results presentation. Med Railway Transport of Ukr. 2004;4:30-8. [Ukrainian].   Norlin M, Wikvall K. Enzymes in the conversion of cholesterol into bile acids. Curr. Mol. Med. 2007;7(2):199-218. CrossRef PubMed   Conservation of the coding regions of the glycine N-acyltransferase gene further suggests that glycine conjugation is an essential detoxification pathway. R. van der Sluis. Gene. 2015;571(1):126-34. CrossRef PubMed   Reichert ZR, Hussain M. Androgen Receptor and Beyond, Targeting Androgen Signaling in Castration-Resistant Prostate Cancer. J Cancer. 2016;22(5):326-29. CrossRef PubMed     CrossRef   Yasui M, Uemura K, Yoneyama S, Kawahara T, Hattori Y, Teranishi J-i, Inoue M, Ohta J-i, Yokomizo Y, Yao M, Uemura H, Miyoshi Y. Predictors of poor response to secondary alternative antiandrogen therapy with flutamide in metastatic castration-resistant prostate cancer. J Clin Oncol. 2016;46(11):1042-46. CrossRef   Kostrubsky SE, Strom SC, Ellis Е, Nelson SD, Abdul E. Mutlib Transport, metabolism, and hepatotoxicity of flutamide, drug-drug interaction with acetaminophen involving phase I and phase II metabolites. Chem Res Toxicol. 2007;20(10):1503-12. CrossRef PubMed   Iwanaga T, Nakakariya М, Yabuuchi Н, Maeda T, Tamai I. Involvement of bile salt export pump in flutamide-induced cholestatic hepatitis. Biol Pharm Bull. 2007;30(4):739-44. CrossRef PubMed   Marin JJ, Macias RI, Briz O, Banales JM, Monte MJ. Bile Acids in Physiology, Pathology and Pharmacology. Curr Drug Metab. 2015;17(1):4-29. CrossRef PubMed

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