Renal transepithelial secretion of ochratoxin A in the non-filtering toad kidney

Toxicology
E BahnemannM Gekle

Abstract

Renal excretion is an important way of elimination for the nephrotoxin ochratoxin A (OTA). Because binding to proteins hinders filtration, excretion is mainly due to proximal tubular secretion. The goal of this study was to investigate the kinetics of secretion as well as the extent of urine and tissue accumulation in situ using the non-filtering amphibian kidney model. Transepithelial secretion is a saturable process (K(m) = 0.63.10(-6) mol/l) and leads to a concentration-dependent accumulation of OTA in the tubular lumen and in renal tissue. Maximum accumulation achieved is approximately 14-fold as compared to the perfusate concentration. There was no accumulation in the tubular lumen as compared to renal tissue (lumen-to-tissue concentration ratio approximately 1). Tissue and tubular lumen accumulation were reduced to approximately 40% of control in the presence of 10(-3) mol/l p-aminohippurate (PAH). Addition of 10(-3) mol/l alpha-ketoglutarate (KG) to PAH-containing perfusate did not lead to a further reduction of secretion. By contrast, addition of 10(-2) mol/l L-phenylalanine (L-Phe) reduced secretion further to approximately 25% of control. In the presence of 10(-3) mol/l probenecid tissue accumulation was reduced to 7%...Continue Reading

References

Nov 14, 1988·Toxicology·C FriisB Hald
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Jan 1, 1996·Kidney & Blood Pressure Research·M Gekle, S Silbernagl

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Citations

Oct 26, 2005·Archives of Toxicology·Jan SchrickxJ Fink-Gremmels
Apr 8, 2011·Zhurnal evoliutsionnoĭ biokhimii i fiziologii·N P Prutskova
Jun 1, 2010·Toxins·Naohiko AnzaiHitoshi Endou
Jan 7, 2005·Molecular Nutrition & Food Research·Michael GekleGerald Schwerdt
Dec 30, 2006·Molecular Nutrition & Food Research·Annie Pfohl-Leszkowicz, Richard A Manderville
Nov 19, 2005·Chemico-biological Interactions·Diana RingotYvan Larondelle
Mar 31, 2009·International Journal of Molecular Sciences·Dragan MilićevićSasa Janković
Oct 1, 2005·The Journal of Pharmacology and Experimental Therapeutics·Daniel A J BowJohn B Pritchard
Aug 16, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Marie-Christin SchulzGerald Schwerdt
Jan 16, 1999·Journal of the American Society of Nephrology : JASN·C E GrovesM Morales

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