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. 2010 Jun;2(6):1381-98.
doi: 10.3390/toxins2061381. Epub 2010 Jun 9.

Molecular mechanism of ochratoxin a transport in the kidney

Naohiko Anzai  1 , Promsuk Jutabha, Hitoshi Endou
Affiliations

Molecular mechanism of ochratoxin a transport in the kidney

Naohiko Anzai et al. Toxins (Basel). 2010 Jun.

Abstract

The mycotoxin, ochratoxin A (OTA), is thought to be responsible for Balkan endemic nephropathy. OTA accumulates in several tissues, especially in the kidneys and liver. The excretion of OTA into urine is thought to be mainly by tubular secretion, presumably via the organic anion transport system. Recently, several families of multispecific organic anion transporters have been identified: organic anion transporters (OATs), organic anion-transporting polypeptides (OATPs), oligopeptide transporters (PEPTs), and ATP-binding cassette (ABC) transporters, such as MRP2 and BCRP. These renal transporters mediate the transmembrane transport of OTA and play a pivotal role in the development of OTA-induced nephrotoxicity.

Keywords: kidney; mycotoxin; nephrotoxicity; ochratoxin A; organic anion transporter.

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Figures

Figure 1
Figure 1
Transport systems for OTA along the nephron. OTA secretion is performed by the proximal tubular organic anion secretion pathway. OTA is reabsorbed along the nephron from apical side. Abbreviations, PT: proximal tubules, TAL: thick ascending limb of the loop of Henle, CD: collecting duct.
Figure 2
Figure 2
Proposed model of organic anion transporters in renal proximal tubules. Abbreviations, OAs: organic anions, DCs: dicarboxylates, MCs: monocarboxylates, GSH: glutathione.
Figure 3
Figure 3
OTA secretion in proximal tubular cells in humans. Organic anion/dicarboxylates (DCs) exchangers OAT1 and OAT3 function as entrance pathways for OTA, and NPT4 and MRP2 may be its exit route in proximal tubular cells. OAT4 at the apical membrane may function as a reabsorptive pathway for OTA. When probenecid (inhibitor of OATs) or PAH (substrate for both OAT1 and OAT3) is coadministered with OTA, they inhibit the tubular secretion of OTA, thus reducing its potential risk.
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