کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9002188 | 1118576 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mechanisms involved in spironolactone-induced choleresis in the rat
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کلمات کلیدی
UGTTuDCBSDFPregnane X-receptorDNP-SGPXRMPMBSEPMrp2AE2CDNBGSSGGSTGSH1-chloro-2,4-dinitrobenzene - 1-کلرو-2،4-دینیتروبنزنUDP-glucuronosyltransferase - UDP-گلوکورونوسیل ترانسفرازSpironolactone - اسپیرونولاکتونbile flow - جریان صفراویmultidrug resistance-associated protein 2 - پروتئین مرتبط با مقاومت چند دارویی 2Bile salt export pump - پمپ صادرات نمک صفرreduced glutathione - کاهش گلوتاتیونGlutathione - گلوتاتیونglutathione S-transferase - گلوتاتیون S-ترانسفرازoxidized glutathione - گلوتاتیون اکسید شده
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Mechanisms involved in spironolactone-induced choleresis in the rat Mechanisms involved in spironolactone-induced choleresis in the rat](/preview/png/9002188.png)
چکیده انگلیسی
The mechanisms involved in spironolactone (SL, 200 μmol/kg body weight, 3 days i.p.)-induced choleresis were explored in vivo by evaluating bile salt export pump (Bsep)-, multidrug resistance-associated protein 2 (Mrp2)-, and anion exchanger 2 (AE2)-mediated secretory processes in rat liver. Hepatic bile salt metabolism was also analyzed. Total bile flow was significantly increased by SL, primarily due to an increase in bile salt-independent bile flow, whereas bile salt secretion was decreased. SL did not produce any choleresis in TRâ rats. SL decreased the de novo bile salt synthesis rate in concordance with impaired microsomal cholesterol 7α-hydroxylase activity, thus leading to a decrease in endogenous bile salt pool size. In contrast, the maximum secretory rate of tauroursodeoxycholate as well as expression of Bsep protein detected by Western blotting were not affected. Thus, decreased bile salt availability for canalicular transport rather than transport capability itself likely explains reduced biliary secretion of bile salts. Biliary secretion of glutathione, an endogenous substrate of Mrp2, and HCO3â, the AE2 substrate, were increased by SL, as a main factor explaining enhanced bile salt-independent bile flow. Western blot studies revealed increased expression of Mrp2 in response to SL whereas AE2 content remained unchanged. Enhanced activity and expression of Mrp2 was confirmed by analyzing the excretion rate of dinitrophenyl S-glutathione, an exogenous substrate of Mrp2, in isolated hepatocytes and by immunofluorescence microscopy, respectively. We conclude that SL increased bile flow mainly by increasing the biliary secretion of glutathione species and HCO3â; increased expression of Mrp2 is also involved.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 69, Issue 3, 1 February 2005, Pages 531-539
Journal: Biochemical Pharmacology - Volume 69, Issue 3, 1 February 2005, Pages 531-539
نویسندگان
MarÃa L. Ruiz, Silvina S. M. Villanueva, Marcelo G. Luquita, Enrique J. Sánchez-Pozzi, Fernando A. Crocenzi, José M. Pellegrino, Justina E. Ochoa, Mary Vore, Aldo D. Mottino, Viviana A. Catania,