• MeSH
• brada MeSH
• injekce MeSH
• kyselina deoxycholová MeSH
• tuková tkáň účinky léků   MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Ortopedie. Chirurgie. Oftalmologie
• NLK Obory
• dermatovenerologie
• farmakoterapie
• NLK Publikační typ
• brožury

• MeSH
• kyseliny cholové terapeutické užití   MeSH
• virové nemoci farmakoterapie   MeSH

• MeSH
• buněčná imunita MeSH
• experimenty na zvířatech MeSH
• kyseliny cholové terapeutické užití   MeSH
• lidé MeSH
• reakce antigenu s protilátkou MeSH
• tvorba protilátek účinky léků   MeSH
• Check Tag
• lidé MeSH

• MeSH
• izotopy diagnostické užití   MeSH
• krysa rodu rattus MeSH
• kyselina deoxycholová MeSH
• myokard MeSH
• myši MeSH
• technecium MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• myši MeSH
• zvířata MeSH

The Pregnane X (PXR), Vitamin D (VDR) and Farnesoid X (FXR) nuclear receptors have been shown to be receptors of bile acids controlling their detoxification or synthesis. Chenodeoxycholic (CDCA) and lithocholic (LCA) acids are ligands of FXR and VDR, respectively, whereas 3-keto and acetylated derivates of LCA have been described as ligands for all three receptors. In this study, we hypothesized that oxidation or acetylation at position 3, 7 and 12 of bile acids DCA (deoxycholic acid), LCA, CA (cholic acid), and CDCA by detoxification enzymes or microbiome may have an effect on the interactions with bile acid nuclear receptors. We employed reporter gene assays in HepG2 cells, the TR-FRET assay with recombinant PXR and RT-PCR to study the effects of acetylated and keto bile acids on the nuclear receptors activation and their target gene expression in differentiated hepatic HepaRG cells. We demonstrate that the DCA 3,12-diacetate and CA 3,7,12-triacetate derivatives are ligands of PXR and DCA 3,12-diacetate induces PXR target genes such as CYP3A4, CYP2B6 and ABCB1/MDR1. In conclusion, we found that acetylated DCA and CA are potent ligands of PXR. Whether the acetylated bile acid derivatives are novel endogenous ligands of PXR with detoxification or physiological functions should be further studied in ongoing experiments.

• MeSH
• acetylace MeSH
• buněčné kultury MeSH
• buňky Hep G2 MeSH
• cytochrom P-450 CYP3A genetika   MeSH
• cytochrom P450 CYP2B6 genetika   MeSH
• hepatocyty účinky léků   enzymologie   metabolismus   MeSH
• kyselina cholová chemie   metabolismus   farmakologie   MeSH
• kyselina deoxycholová chemie   metabolismus   farmakologie   MeSH
• lidé MeSH
• ligandy MeSH
• myši MeSH
• oxidace-redukce MeSH
• P-glykoprotein genetika   MeSH
• plazmidy MeSH
• receptory cytoplazmatické a nukleární chemie   genetika   metabolismus   MeSH
• receptory kalcitriolu chemie   genetika   metabolismus   MeSH
• reportérové geny MeSH
• simulace molekulového dockingu MeSH
• steroidní receptory chemie   genetika   metabolismus   MeSH
• techniky dvojhybridového systému MeSH
• transfekce MeSH
• vazba proteinů MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• chromatin MeSH
• kyselina deoxycholová analogy a deriváty   aplikace a dávkování   farmakologie   MeSH
• myši MeSH
• radiační účinky MeSH
• rozpustnost MeSH
• thymus MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH

Amphotericin B deoxycholate (AmB) or Amphotericin B colloidal dispersion (ABCD) are used in clinics for the treatment of systemic fungal infections. The goal of our study was to compare the nephrotoxicity of these drugs in rat kidney. The effects of AmB and ABCD on the ultrastructure of the epithelium of renal tubules were studied and evaluated using morphometric and statistical methods. Two groups of 3 animals were established: group 1 was treated with AmB desoxycholate and group 2, to which ABCD was applied. AmB caused more than ABCD ultrastructural changes in the cytoplasm of the epithelial cells: damage to mitochondria, vacuolation of cytoplasm, and increased values of volume density of peroxisomes. However, we failed to observe significant differences in morphology and density of the other cell organelles. The proximal tubules seemed to be more sensitive to the nephrotoxic influence of both formulas than the distal tubules of rat kidney. Although, AmB causes more severe damage than ABCD, both drugs cause damage to renal tubuli.

• MeSH
• amfotericin B toxicita   MeSH
• antifungální látky toxicita   MeSH
• epitel účinky léků   ultrastruktura   MeSH
• fixní kombinace léků MeSH
• krysa rodu rattus MeSH
• kyselina deoxycholová toxicita   MeSH
• ledvinové kanálky účinky léků   ultrastruktura   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• Escherichia coli MeSH
• Francisella MeSH
• kyselina deoxycholová analogy a deriváty   MeSH
• lipopolysacharidy MeSH
• molekulární biologie MeSH
• teplota MeSH

Amphotericin B (AmB) is excreted via the renal excretion route. This excretion process may result in nephrotoxicity. However, relevant information on the precise renal excretion mechanisms is not available. The aim of the study was to analyze the possible interaction of AmB or its prodrug AmB deoxycholate (AmB-DOC) with the typical renal organic anion transporters (OATs) and organic cation transporters (OCTs), using cellular and organ models. The relevant transport systems were then investigated in terms of the drug-drug interactions of AmB-DOC with antivirals that might potentially be used concomitantly. To analyze the renal excretion mechanisms of [(3)H]AmB, perfused rat kidney was employed. HeLa and MDCK II cells transiently transfected with human OAT1 (hOAT1) or hOCT2 were used as the cellular models. A significant tubular secretion of AmB was demonstrated in the perfused rat kidney. The cellular studies performed confirmed the active transport of AmB into cells. AmB did not interact with hOAT1 but strongly inhibited hOCT2. In contrast, AmB-DOC inhibited both hOAT1 and hOCT2. However, [(3)H]AmB cellular uptake by hOAT1 and hOCT2 was not found. AmB-DOC interacted significantly with adefovir, tenofovir, and cidofovir in hOAT1-transfected cells at supratherapeutic concentrations. In conclusion, the significant potency of AmB and AmB-DOC for inhibiting the transporters was demonstrated in this study. The secretion of AmB in the renal tubules is likely not related to the transporters here, since the drug was not proven to be a substrate for them. Drug-drug interactions of AmB and the antivirals used in this study on the investigated transporters are not probable.

• MeSH
• amfotericin B metabolismus   MeSH
• antivirové látky metabolismus   MeSH
• buněčné linie MeSH
• fixní kombinace léků MeSH
• HeLa buňky MeSH
• krysa rodu rattus MeSH
• kyselina deoxycholová metabolismus   MeSH
• ledviny metabolismus   MeSH
• lékové interakce MeSH
• lidé MeSH
• potkani Wistar MeSH
• protein 1 přenášející organické anionty metabolismus   MeSH
• proteiny přenášející organické kationty metabolismus   MeSH
• psi MeSH
• teplota MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• jaterní cirhóza farmakoterapie   MeSH
• kyselina deoxycholová farmakologie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH