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Toxins 2015, 7(4), 1005-1017; doi:10.3390/toxins7041005

Contribution of Organ Vasculature in Rat Renal Analysis for Ochratoxin A: Relevance to Toxicology of Nephrotoxins

1
Centre for Environmental Policy, Imperial College London, London SW7 2AZ, UK
2
Molecular Biology Section, Department of Biology, Science Faculty, Akdeniz University, Antalya 07058, Turkey
3
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Mehmet Akif Ersoy University, Burdur 15030, Turkey
4
Department of Pathology, Faculty of Veterinary Medicine, Mehmet Akif Ersoy University, Burdur 15030, Turkey
*
Author to whom correspondence should be addressed.
Academic Editor: Richard A. Manderville
Received: 10 November 2014 / Revised: 12 December 2014 / Accepted: 17 March 2015 / Published: 24 March 2015
(This article belongs to the Section Mycotoxins)
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Abstract

Assumptions surrounding the kidney as a target for accumulation of ochratoxin A (OTA) are addressed because the contribution of the toxin in blood seems invariably to have been ignored. Adult rats were maintained for several weeks on toxin-contaminated feed. Using standard perfusion techniques, animals were anaesthetised, a blood sample was taken, one kidney was ligated, and the other kidney perfused with physiological saline in situ under normal blood pressure. Comparative analysis of OTA in pairs of kidneys showed marked reduction in the perfused organ in the range 37%–98% (mean 75%), demonstrating the general efficiency of perfusion supported also by histology, and implying a major role of blood in the total OTA content of kidney. Translation of OTA values in plasma to whole blood, and its predicted contribution as a 25% vascular compartment in kidney gave values similar to those in non-perfused kidneys. Thus, apparent ‘accumulation’ of OTA in kidney is due to binding to plasma proteins and long half-life in plasma. Attention should be re-focused on whole animal pharmacokinetics during chronic OTA exposure. Similar principles may be applied to DNA-OTA adducts which are now recognised as occurring in blood; application could also extend to other nephrotoxins such as aristolochic acid. Thus, at least, quantitative reassessment in urological tissues seems necessary in attributing adducts specifically as markers of potentially-tumourigenic exposure. View Full-Text
Keywords: perfusion in vivo; ochratoxin A; renal vasculature; ochratoxin accumulation; DNA adducts; aristolochic acid perfusion in vivo; ochratoxin A; renal vasculature; ochratoxin accumulation; DNA adducts; aristolochic acid
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mantle, P.; Kilic, M.A.; Mor, F.; Ozmen, O. Contribution of Organ Vasculature in Rat Renal Analysis for Ochratoxin A: Relevance to Toxicology of Nephrotoxins. Toxins 2015, 7, 1005-1017.

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