![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 280, Issue 1, 220-224, 1997
Physiologisches Institut, Universität Würzburg,
D-97070 Würzburg, Germany
Ochratoxin A (OTA) is a widespread nephrotoxin excreted to a
substantial degree via the kidney. We investigated whether
[3H]OTA is reabsorbed from the tubular lumen along the
nephron and thus recycles within the kidney. Superficial early proximal
and early distal tubules of male Wistar rats were micropunctured
in situ. Microinfusion of OTA into superficial nephrons
showed that it was reabsorbed in proximal as well as distal parts of
the nephron. Reabsorption during early distal microinfusion was not
saturable in the range of 0 to 5·10
4 mol/liter and
accounted for 20% of OTA infused. Reabsorption during early proximal
microinfusion was partially saturable and reached values up to 70% of
OTA infused. The apparent Km for OTA reabsorption was 236·106 mol/liter and maximum
transport rate 970 fmol/min/nephron. OTA reabsorption was pH dependent
and decreased from 70 to 40% during proximal infusion and from 20 to
10% during distal infusion when pH increased from 6.0 to 7.4. The
dipeptides carnosine and glyclysarcosine reduced OTA reabsorption
significantly. L-Phenylalanine showed no significant
inhibitory action. From our results we conclude: 1) there is
substantial reabsorption of OTA along the nephron; 2) one-third of
reabsorption takes place in the distal tubule and/or the collecting
duct, two-thirds in the proximal tubule; 3) "distal" reabsorption
can be explained at least in part by nonionic diffusion, because it was
not saturable but pH dependent; 4) "proximal" reabsorption was in
part mediated by the H+-dipeptide cotransporter; 5)
reabsorption of filtered and secreted OTA delays its excretion and may
lead to accumulation of the toxin in renal tissue and 6) inhibition of
OTA reabsorption (e.g., by urine alkalinization) should
help to accelerate OTA excretion and thus reduce its toxicity.
This article has been cited by other articles:
|
|
 |
|
  G. Schwerdt, R. Freudinger, C. Schuster, F. Weber, O. Thews, and M. Gekle Cisplatin-Induced Apoptosis Is Enhanced by Hypoxia and by Inhibition of Mitochondria in Renal Collecting Duct Cells Toxicol. Sci., May 1, 2005; 85(1): 735 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Blank and S. Wolffram Alkalinization of Urinary pH Accelerates Renal Excretion of Ochratoxin A in Pigs J. Nutr., September 1, 2004; 134(9): 2355 - 2358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tsuda, T. Sekine, M. Takeda, S. H. Cha, Y. Kanai, M. Kimura, and H. Endou Transport of Ochratoxin A by Renal Multispecific Organic Anion Transporter 1 J. Pharmacol. Exp. Ther., June 1, 1999; 289(3): 1301 - 1305. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. E. GROVES, G. NOWAK, and M. MORALES Ochratoxin A Secretion in Primary Cultures of Rabbit Renal Proximal Tubule Cells J. Am. Soc. Nephrol., January 1, 1999; 10(1): 13 - 20. [Abstract] [Full Text]
|
|
|
|
|
|
A. Dahlmann, W. H. Dantzler, S. Silbernagl, and M. Gekle Detailed Mapping of Ochratoxin A Reabsorption Along the Rat Nephron In Vivo: The Nephrotoxin Can Be Reabsorbed in All Nephron Segments by Different Mechanisms J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 157 - 162. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
