دورية أكاديمية
Anticholestatic mechanisms of ursodeoxycholic acid in lipopolysaccharide-induced cholestasis.
| العنوان: | Anticholestatic mechanisms of ursodeoxycholic acid in lipopolysaccharide-induced cholestasis. |
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| المؤلفون: | Razori MV; Institute of Experimental Physiology (IFISE), Faculty of Biochemical and Pharmaceutical Sciences of the National University of Rosario, 2000 Rosario, Argentina., Maidagan PM; Institute of Experimental Physiology (IFISE), Faculty of Biochemical and Pharmaceutical Sciences of the National University of Rosario, 2000 Rosario, Argentina., Ciriaci N; Institute of Experimental Physiology (IFISE), Faculty of Biochemical and Pharmaceutical Sciences of the National University of Rosario, 2000 Rosario, Argentina., Andermatten RB; Institute of Experimental Physiology (IFISE), Faculty of Biochemical and Pharmaceutical Sciences of the National University of Rosario, 2000 Rosario, Argentina., Barosso IR; Institute of Experimental Physiology (IFISE), Faculty of Biochemical and Pharmaceutical Sciences of the National University of Rosario, 2000 Rosario, Argentina., Martín PL; Institute of Experimental Physiology (IFISE), Faculty of Biochemical and Pharmaceutical Sciences of the National University of Rosario, 2000 Rosario, Argentina., Basiglio CL; Institute of Experimental Physiology (IFISE), Faculty of Biochemical and Pharmaceutical Sciences of the National University of Rosario, 2000 Rosario, Argentina., Sánchez Pozzi EJ; Institute of Experimental Physiology (IFISE), Faculty of Biochemical and Pharmaceutical Sciences of the National University of Rosario, 2000 Rosario, Argentina., Ruiz ML; Institute of Experimental Physiology (IFISE), Faculty of Biochemical and Pharmaceutical Sciences of the National University of Rosario, 2000 Rosario, Argentina., Roma MG; Institute of Experimental Physiology (IFISE), Faculty of Biochemical and Pharmaceutical Sciences of the National University of Rosario, 2000 Rosario, Argentina. Electronic address: mroma@fbioyf.unr.edu.ar. |
| المصدر: | Biochemical pharmacology [Biochem Pharmacol] 2019 Oct; Vol. 168, pp. 48-56. Date of Electronic Publication: 2019 Jun 13. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Original Publication: Oxford, New York [etc.] Paragamon Press. |
| مواضيع طبية MeSH: | Cholagogues and Choleretics/*therapeutic use , Cholestasis/*chemically induced , Cholestasis/*drug therapy , Lipopolysaccharides/*pharmacology , Ursodeoxycholic Acid/*therapeutic use, ATP Binding Cassette Transporter, Subfamily B, Member 11/metabolism ; ATP-Binding Cassette Transporters/metabolism ; Alkaline Phosphatase/blood ; Animals ; Bile Acids and Salts/metabolism ; Cholagogues and Choleretics/administration & dosage ; Cholagogues and Choleretics/pharmacology ; Disease Models, Animal ; Hepatocytes/drug effects ; Hepatocytes/metabolism ; Liver/metabolism ; Male ; Rats ; Rats, Wistar ; Treatment Outcome ; Ursodeoxycholic Acid/administration & dosage ; Ursodeoxycholic Acid/pharmacology |
| مستخلص: | Lipopolysaccharide (LPS) from Gram (-) bacteria induces inflammatory cholestasis by impairing the expression/localization of transporters involved in bile formation (e.g., Bsep, Mrp2). Therapeutic options for this disease are lacking. Ursodeoxycholic acid (UDCA) is the first choice therapy in cholestasis, but its anticholestatic efficacy in this hepatopathy remains to be evaluated. To asses it, male Wistar rats received UDCA for 5 days (25 mg/Kg/day, i.p.) with or without LPS, administered at 8 a.m. of the last 2 days (4 mg/Kg/day, i.p.), plus half of this dose at 8 p.m. of the last day. Then, plasma alkaline phosphatase (ALP), bile flow, basal and taurocholate-stimulated bile acid output, total glutathione output, and total/plasma membrane liver protein expression of Bsep and Mrp2 by confocal microscopy were assessed. mRNA levels of both transporters were assessed by Real-Time PCR. Plasma pro-inflammatory cytokines (IL-6 and TNF-α) were measured by ELISA. Our results showed that UDCA attenuated LPS-induced ALP plasma release and the impairment in the excretion of the Bsep substrate, taurocholate. This was associated with an improved Bsep expression at both mRNA and protein levels, and by an improved localization of Bsep in plasma membrane. UDCA failed to reduce the increase in plasma pro-inflammatory cytokines induced by LPS and Mrp2 expression/function. In conclusion, UDCA protects the hepatocyte against the damaging effect of bile acids accumulated by the LPS-induced secretory failure. This involved an enhanced synthesis of Bsep and an improved membrane stability of the newly synthesized transporters. (Copyright © 2019 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Bile acid export pump; Bile acids; Hepatocellular transporters; Lipopolysaccharide-induced cholestasis; Ursodeoxycholic acid |
| المشرفين على المادة: | 0 (ATP Binding Cassette Transporter, Subfamily B, Member 11) 0 (ATP-Binding Cassette Transporters) 0 (Abcb11 protein, rat) 0 (Abcc2 protein, rat) 0 (Bile Acids and Salts) 0 (Cholagogues and Choleretics) 0 (Lipopolysaccharides) 724L30Y2QR (Ursodeoxycholic Acid) EC 3.1.3.1 (Alkaline Phosphatase) |
| تواريخ الأحداث: | Date Created: 20190617 Date Completed: 20200713 Latest Revision: 20200713 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.bcp.2019.06.009 |
| PMID: | 31202734 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-2968 |
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| DOI: | 10.1016/j.bcp.2019.06.009 |