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World J Gastroenterol. Nov 28, 2012; 18(44): 6387-6397
Published online Nov 28, 2012. doi: 10.3748/wjg.v18.i44.6387
Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis
Anabel Brandoni, María Herminia Hazelhoff, Romina Paula Bulacio, Adriana Mónica Torres
Anabel Brandoni, María Herminia Hazelhoff, Romina Paula Bulacio, Adriana Mónica Torres, Pharmacology Unit, Department of Physiological Sciences, Faculty of Biochemical and Pharmaceutical Sciences, National University of Rosario, the National Scientific and Technical Research Council, 2000 Rosario, Argentine
Author contributions: Brandoni A, Hazelhoff MH, Bulacio RP, Torres AM all contributed to this work.
Supported by Grants from FONCYT (PICT 2007, No. 00966, PICT 2010, No. 2127); CONICET (PIP 2009-2011, No. 1665, PIP 2012-2015, No. 00014); UNR PID (2008-2011/2012-2015)
Correspondence to: Adriana Mónica Torres, PhD, Professor of Pharmacology, Pharmacology Unit, Department of Physiological Sciences, Faculty of Biochemical and Pharmaceutical Sciences, National University of Rosario, the National Scientific and Technical Research Council, Suipacha 531, 2000 Rosario, Argentina. admotorres@yahoo.com.ar
Telephone: +54-341-4373787 Fax: +54-341-4804598
Received: May 7, 2012
Revised: June 18, 2012
Accepted: June 28, 2012
Published online: November 28, 2012
Abstract

Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct. The absorption, distribution and elimination of drugs are impaired during this pathology. Prolonged cholestasis may alter both liver and kidney function. Lactam antibiotics, diuretics, non-steroidal anti-inflammatory drugs, several antiviral drugs as well as endogenous compounds are classified as organic anions. The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds. It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions. The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis, such as multidrug resistance-associated protein 2, organic anion transporting polypeptide 1, organic anion transporter 3, bilitranslocase, bromosulfophthalein/bilirubin binding protein, organic anion transporter 1 and sodium dependent bile salt transporter. The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.

Keywords: Organic anions; Liver; Kidney; Multidrug resistance-associated protein 2; Organic anion transporting polypeptide 1; Organic anion transporter 3; Bilitranslocase; Bromosulfophthalein/bilirubin binding protein; Organic anion transporter 1; Sodium dependent bile salt transporter