کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9244135 | 1209903 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Complementary Stimulation of Hepatobiliary Transport and Detoxification Systems by Rifampicin and Ursodeoxycholic Acid in Humans
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کلمات کلیدی
DCABAATMDRPBCCyPUGTHCAMRPUDCAOATPBSEPCDCAHDCA7α-hydroxy-4-cholesten-3-one - 7α-هیدروکسی 4-کلستین-3-یکuridine diphosphate glucuronosyltransferase - uridine دی فسفات گلوکورونوزیل ترانسفرازLCA - ارزیابی چرخه حیاتChenodeoxycholic acid - اسید ChenodeoxycholicDeoxycholic acid - اسید DeoxycholicLithocholic acid - اسید لیتاکولیکHyodeoxycholic acid - اسید هیودوکسوخیکلhyocholic acid - اسید هیوکولارCholic acid - اسید چلیکUrsodeoxycholic acid - اورسودوکسی کولیک اسید، اورسودیولRifampicin - ریفامپینCytochrome P450 - سیتوکروم پی۴۵۰Primary biliary cirrhosis - سیروز صفراوی اولیهMultidrug resistance-related protein - پروتئین مرتبط با مقاومت چند داروییmultidrug resistance protein - پروتئین مقاوم در برابر چندین رژیمOrganic anion transporting polypeptide - پلیپپتید حمل آنیون ارگانیکBile salt export pump - پمپ صادرات نمک صفر
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: Rifampicin (RIFA) and ursodeoxycholic acid (UDCA) improve symptoms and biochemical markers of liver injury in cholestatic liver diseases by largely unknown mechanisms. We aimed to study the molecular mechanisms of action of these drugs in humans.
Methods: Thirty otherwise healthy gallstone patients scheduled for cholestectomy were randomized to RIFA (600 mg/day for 1 week) or UDCA (1 g/day for 3 weeks) or no medication before surgery. Routine biochemistry, lipids, and surrogate markers for P450 activity (4β-hydroxy cholesterol, 4β-OH-C) and bile acid synthesis (7α-hydroxy-4-cholesten-3-one, C-4) were measured in serum. Bile acids were analyzed in serum, urine, and bile. A wedge liver biopsy specimen was taken to study expression of hepatobiliary ABC transporters as well as detoxification enzymes and regulatory transcription factors.
Results: RIFA enhanced bile acid detoxification as well as bilirubin conjugation and excretion as reflected by enhanced expression of CYP3A4, UGT1A1, and MRP2. These molecular effects were paralleled by decreased bilirubin and deoxycholic acid concentrations in serum and decreased lithocholic and deoxycholic acid concentrations in bile. UDCA on the other hand stimulated the expression of BSEP, MDR3, and MRP4. UDCA became the predominant bile acid after UDCA treatment and lowered the biliary cholesterol saturation index.
Conclusions: RIFA enhances bile acid detoxification as well as bilirubin conjugation and export systems, whereas UDCA stimulates the expression of transporters for canalicular and basolateral bile acid export as well as the canalicular phospholipid flippase. These independent but complementary effects may justify a combination of both agents for the treatment of cholestatic liver diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 129, Issue 2, August 2005, Pages 476-485
Journal: Gastroenterology - Volume 129, Issue 2, August 2005, Pages 476-485
نویسندگان
Hanns-Ulrich Marschall, Martin Wagner, Gernot Zollner, Peter Fickert, Ulf Diczfalusy, Judith Gumhold, Dagmar Silbert, Andrea Fuchsbichler, Lisbet Benthin, Rosita Grundström, Ulf Gustafsson, Staffan Sahlin, Curt Einarsson, Michael Trauner,