Elsevier

Toxicology

Volume 52, Issues 1–2, 14 November 1988, Pages 209-217
Toxicology

Uptake of ochratoxin A by slices of pig kidney cortex

https://doi.org/10.1016/0300-483X(88)90205-3Get rights and content

Abstract

Ochratoxin A (OCT A) is a nephrotoxin causing selective necrosis of the proximal tubule. Being an organic anion OCT A might be expected to enter the tubule cells by the organic anion transport system. Pig renal cortical slices were used to characterize the OCT A transport. OCT A (5 × 10−3 mM) was accumulated against a concentration gradient with a slice to medium ratio of 8.9 ± 2.9 in the presence of oxygen. This accumulation was markedly reduced in a nitrogen atmosphere (S/M ratio = 2.9 ± 0.5). OCT A accumulation was dependent on medium concentration. With increasing concentration (5 × 10−4–5 × 10−1 mM), slice to medium ratio initially rose from 6.9 ± 2.0 to 11.7 ± 1.2 whereupon it declined to 5.4 ± 1.1. This pattern indicates that both carrier mediated transport and intracellular metabolism may contribute to the net accumulation of the toxin. OCT A (10−4 to 1 mM) inhibited p-aminohippurate (PAH) and phenolsulphophthalein (PSP) uptake in a dose-dependent manner. Up to 10−1 mM, OCT A did not inhibit acetylation of PAH suggesting that aerobic metabolism and the energy supply for the transport process were unaffected. Kinetic studies revealed a competitive inhibition of the PSP transport. It is concluded that OCT A enters the proximal tubule cells by the common organic anion transport system.

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