Molecular Mechanism of Ochratoxin A Transport in the Kidney

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.

Ochratoxin A kinetics: A review of analytical methods and studies in rat model

“…The localization, molecular and functional characteristics, and substrate and inhibitor specificity of the main organic anion transporters have been extensively reviewed (Russel et al, 2002;Wang and Sweet, 2013). These specific transporters may also be involved in the accumulation of OTA in organs other than kidney (Anzai et al, 2010, Eckhardt et al, 1999Kontaxi et al, 1996, O'Brien and. It is also important to highlight that OTA kidney uptake and handling of OTA by OATs is dependent on the OTA bound to plasma protein (Bow et al, 2006).…”

A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin A

“…Within the body, OTxA accumulates in several tissues, especially in the kidney and liver, and is excreted mainly from the kidney (5). An in vivo study revealed that probenecid (a typical inhibitor of the renal organic anion transporters) decreased the renal clearance of OTxA (6). Studies using isolated renal tubules showed that the organic anion transport system mediates the uptake of OTxA and may play a role in OTxA toxicity (6).…”

“…An in vivo study revealed that probenecid (a typical inhibitor of the renal organic anion transporters) decreased the renal clearance of OTxA (6). Studies using isolated renal tubules showed that the organic anion transport system mediates the uptake of OTxA and may play a role in OTxA toxicity (6). Thus, the excretion of OTxA into urine is likely to be mainly by tubular secretion, presumably via the organic anion transport system (7).…”

“…The excretion of numerous organic anions, including endogenous metabolites and drugs as well as toxic xenobiotics, is an important physiological function of renal proximal tubules (6,8,9). The process of excreting organic anions through proximal tubular cells is achieved via unidirectional transcellular transport, involving the uptake of organic anions into cells from the blood across the basolateral membrane, followed by extrusion across the apical membrane into the tubular lumen.…”

“…The process of excreting organic anions through proximal tubular cells is achieved via unidirectional transcellular transport, involving the uptake of organic anions into cells from the blood across the basolateral membrane, followed by extrusion across the apical membrane into the tubular lumen. To date, four isoforms of human organic anion transporters (hOATs: hOAT1 to 4) have been identified in the kidneys (6). Since OTxA has anionic moieties (1), it is classified as an organic anion and requires transporters for membrane permeation.…”