Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced Nephrotoxicity

In the present review we have attempted to assess the involvement of the organic anion transporters OAT1, OAT2, OAT3, and OAT4, belonging to the SLC22 family of polyspecific carriers, in drug-induced renal damage in humans. We have focused on drugs with widely recognized nephrotoxic potential, which...

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Main Authors: Natascha A. Wolff, Yohannes Hagos
Format: Article
Language:English
Published: MDPI AG 2010-08-01
Series:Toxins
Subjects:
Online Access:http://www.mdpi.com/2072-6651/2/8/2055/
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spelling doaj-f04acf80e1be4c8c85de23afd551e9d32020-11-25T00:23:53ZengMDPI AGToxins2072-66512010-08-01282055208210.3390/toxins2082055Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced NephrotoxicityNatascha A. WolffYohannes HagosIn the present review we have attempted to assess the involvement of the organic anion transporters OAT1, OAT2, OAT3, and OAT4, belonging to the SLC22 family of polyspecific carriers, in drug-induced renal damage in humans. We have focused on drugs with widely recognized nephrotoxic potential, which have previously been reported to interact with OAT family members, and whose underlying pathogenic mechanism suggests the participation of tubular transport. Thus, only compounds generally believed to cause kidney injury either by means of direct tubular toxicity or crystal nephropathy have been considered. For each drug, or class of agents, the evidence for actual transport mediated by individual OATs under in vivo conditions is discussed. We have then examined their role in the context of other carriers present in the renal proximal tubule sharing certain substrates with OATs, as these are critical determinants of the overall contribution of OAT-dependent transport to intracellular accumulation and transepithelial drug secretion, and thus the impact it may have in drug-induced nephrotoxicity. http://www.mdpi.com/2072-6651/2/8/2055/drug-induced nephrotoxicitytubular cell toxicitynephrolithiasisOAT1OAT2OAT3OAT4
collection DOAJ
language English
format Article
sources DOAJ
author Natascha A. Wolff
Yohannes Hagos
spellingShingle Natascha A. Wolff
Yohannes Hagos
Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced Nephrotoxicity
Toxins
drug-induced nephrotoxicity
tubular cell toxicity
nephrolithiasis
OAT1
OAT2
OAT3
OAT4
author_facet Natascha A. Wolff
Yohannes Hagos
author_sort Natascha A. Wolff
title Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced Nephrotoxicity
title_short Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced Nephrotoxicity
title_full Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced Nephrotoxicity
title_fullStr Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced Nephrotoxicity
title_full_unstemmed Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced Nephrotoxicity
title_sort assessment of the role of renal organic anion transporters in drug-induced nephrotoxicity
publisher MDPI AG
series Toxins
issn 2072-6651
publishDate 2010-08-01
description In the present review we have attempted to assess the involvement of the organic anion transporters OAT1, OAT2, OAT3, and OAT4, belonging to the SLC22 family of polyspecific carriers, in drug-induced renal damage in humans. We have focused on drugs with widely recognized nephrotoxic potential, which have previously been reported to interact with OAT family members, and whose underlying pathogenic mechanism suggests the participation of tubular transport. Thus, only compounds generally believed to cause kidney injury either by means of direct tubular toxicity or crystal nephropathy have been considered. For each drug, or class of agents, the evidence for actual transport mediated by individual OATs under in vivo conditions is discussed. We have then examined their role in the context of other carriers present in the renal proximal tubule sharing certain substrates with OATs, as these are critical determinants of the overall contribution of OAT-dependent transport to intracellular accumulation and transepithelial drug secretion, and thus the impact it may have in drug-induced nephrotoxicity.
topic drug-induced nephrotoxicity
tubular cell toxicity
nephrolithiasis
OAT1
OAT2
OAT3
OAT4
url http://www.mdpi.com/2072-6651/2/8/2055/
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