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Výsledky projektu Role deficitu železa a Mrp2 transportéru v rozvoji estrogeny-indukované cholestázy

Výsledky

▼▲Typ výsledku ▼▲Autor celku ▼▲Název celku
(Celkem 6 zázn.)
Alaei Faradonbeh, Fatemeh; Lastuvkova, Hana; Cermanova, Jolana; Hroch, Milos; Nova, Zuzana; Uher, Martin; Hirsova, Petra; Pavek, Peter; Micuda, Stanislav . Multidrug Resistance-Associated Protein 2 Deficiency Aggravates Estrogen-Induced Impairment of Bile Acid Metabolomics in Rats. Frontiers in Physiology, 2022, sv. (Lipid and Fatty Acid Research), s. 1–16. ISSN 1664-042X. IF 4.56. [Článek v časopise]
Our project's final evaluation, GAUK 556218, was postponed because we promised further publication. I attach it now to complete our report.
Prasnicka, Alena; Lastuvkova, Hana; Alaei Faradonbeh, Fatemeh; Cermanova, Jolana; Hroch, Milos; Mokry, Jaroslav; Dolezelova, Eva; Pavek, Petr; Zizalova, Katerina; Vitek, Libor; Nachtigal, Petr; Micuda, Stanislav. . Iron overload reduces synthesis and elimination of bile acids in rat liver. Scientific Reports, 2019, sv. 9, s. 1–12. ISSN 2045-2322. IF 3.998. [Článek v časopise]
During the first year of the project, we also finished preparation for the project solution by resolving the iron-overload study with the introduction of all necessary methods for the current study. Results have been published in Scientific Reports journal (IF (3.9) - article is enclosed. Thus, the project with proper affiliation to the Charles University and dedication to the Grant Agency of the Charles University has been presented in one paper, and the second is under revision. The third manuscript focusing on core results of the project, i.e. iron depletion and bile acid homeostasis during estrogen-induced cholestasis, will be completed this year (2021).
Alaei Faradonbeh, Fatemeh; Igreja Sae, Ivone; Lastuvkova, Hana; Cermanova, Jolana; Hroch, Milos; Faistova, Hana; Mokry, Jaroslav; Nova,Zuzana; Uher, Martin; Nachtigal, Petr; Pavek, Petr., We introduced a mice model of ethinylestradiol-induced cholestasis as preparation for the possibility of using Mrp2-deficient mice, which are accessible on the market. These data were summarized and send as a manuscript to Chemico-Biological Interactions (IF 3.7) journal, where it passes first evaluation and reviewers demanded just minor modification - the manuscript is enclosed. [Jiný výsledek]
Alaei Faradonbeh, Fatemeh; Lastuvkova, Hana; Cermanova, Jolana; Hroch, Milos; Nova,Zuzana; Nachtigal, Petr; Pavek, Petr., In EE/ID-EE groups: 1- (ethinylestradiol) 1-increased plasma BA – Iron depletion is a risk factor for cholestasis 2-Bile secretion of bile acids BA unchanged but Cyp7a1 which is one of the major bile acid synthesis enzymes is increased. reduced bile flow mainly by reduced Bile secretion of glutathione - due to reduced Mrp2 In TR/TR-EE groups: 1-Plasma bile acid was unchanged 2-Bile secretion of bile acids reduced due to reduction of Ntcp / Bsep transporters and also bile synthesis enzymes such as Cyp7a1 and Cyp8b1. Iron depletion and Mrp2 deficiency worsen the ethinylestradiol-induced cholestasis. note: EE(ethinylestradiol), ID(iron depletion diet), TR(Mrp2 negative Rats). [Jiný výsledek]
Alaei Faradonbeh-Fatemeh, Figure 1. Ethinylestradiol (EE) induced significant impairment of bile flow in both wild-type Lewis rats (LW) and Mrp2-deficient rats (TR, transporter restricted). Iron depletion (ID) induced by diet applied over 21 days produced discrepant bile flow changes in WT, and TR animals. However, simultaneous iron depletion and EE administration led to worsening of EE-induced cholestasis in LW as well as in TR female rats. ***P < 0.001. Figure 2. Metformin (M) increased bile flow in vehicle (P) treated female mice, while it reduced this parameter in ethinylestradiol-administered (EE) group. *P < 0.05 , ***P < 0.001 vs vehicle treated group (P); †††P < 0.001 vs. EE group. [Jiný výsledek]
Alaei Faradonbeh Fatemeh, Female Lewis rats healthy (LW) or Mrp2-deficient (TR) with standard (chow) or iron-deficient (ID) diet with or without administration of ethinylestradiol (EE) were used in this study. The animals were divided into eight different groups (see below): 1- LW-chow 2- LW-ID 3- LW- chow-EE 4- LW-ID-EE 5- TR-chow 6- TR-ID 7- TR-chow-EE 8- TR-ID-EE It has been shown clearly what is the effect of standard and ID diet, and also EE administration on each of the biochemistry parameters (ALT, AST, Bilirubin, Total Cholesterol) in first four graphs as well as you can see the effect of the standard and ID diet, and also EE administration on bile flow in different groups of animals in the last graph. [Jiný výsledek]