title: Contribution of organ vasculature in rat renal analysis for ochratoxin a: relevance to toxicology of nephrotoxins.
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.
authors: Centre for Environmental Policy, Imperial College London, London SW7 2AZ, UK. p.mantle@imperial.ac.uk.
authors: Peter
authors: P
authors: Mantle
authors: Molecular Biology Section, Department of Biology, Science Faculty, Akdeniz University, Antalya 07058, Turkey. mkilic@akdeniz.edu.tr.
authors: Mehmet A
authors: MA
authors: Kilic
authors: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Mehmet Akif Ersoy University, Burdur 15030, Turkey. fmor@mehmetakif.edu.tr.
authors: Firdevs
authors: F
authors: Mor
authors: Department of Pathology, Faculty of Veterinary Medicine, Mehmet Akif Ersoy University, Burdur 15030, Turkey. ozlemozmen@mehmetakif.edu.tr.
authors: Ozlem
authors: O
authors: Ozmen
mesh_terms: D000818:Animals; D005260:Female; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D009793:Ochratoxins / Q000097:blood / Q000493:pharmacokinetics*; D010477:Perfusion; D017208:Rats, Wistar
chemical_list: D009793:Ochratoxins; C025589:ochratoxin A