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Contribution of organ vasculature in rat renal analysis for ochratoxin a: relevance to toxicology of nephrotoxins.

Mantle P, Kilic MA, Mor F, Ozmen O - Toxins (Basel) (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Environmental Policy, Imperial College London, London SW7 2AZ, UK. p.mantle@imperial.ac.uk.

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.

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Kidney perfusion efficiency in rats receiving dietary ochratoxin A; contrasting sections stained with haematoxylin and eosin. (A) Not perfused; medullary blood vessels filled with erythrocytes (arrows); (B) Moderately efficient perfusion; numerous erythrocytes (arrows) in the medullary blood vessels; (C) Efficiently perfused kidney, no erythrocytes in the cortical blood vessels and glomeruli; (D) Efficiently perfused kidney; medullary blood vessels empty. Bar = 100 μm.
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toxins-07-01005-f001: Kidney perfusion efficiency in rats receiving dietary ochratoxin A; contrasting sections stained with haematoxylin and eosin. (A) Not perfused; medullary blood vessels filled with erythrocytes (arrows); (B) Moderately efficient perfusion; numerous erythrocytes (arrows) in the medullary blood vessels; (C) Efficiently perfused kidney, no erythrocytes in the cortical blood vessels and glomeruli; (D) Efficiently perfused kidney; medullary blood vessels empty. Bar = 100 μm.

Mentions: The study focuses on the situation within individuals and therefore tabulated findings (Table 1) show both individual data and gender group means where relevant. Generally, the measured OTA values in plasma were seven- to eight-fold higher than those in the normal (non-perfused) kidney. Qualitative monitoring of technical efficiency of flushing blood from the renal vasculature (Figure 1), assessed by histology of a small portion of each perfused kidney, clearly demonstrated the degree of success according to the reduction in the erythrocyte population that is naturally abundant in non-perfused kidney (Figure 1A). There was consistent correlation between the degree of perfusion efficiency predicted from histology (Figure 1B–D) and the percent efficiency values calculated from subsequent measurement of OTA in the perfused organs are described below (Table 1).


Contribution of organ vasculature in rat renal analysis for ochratoxin a: relevance to toxicology of nephrotoxins.

Mantle P, Kilic MA, Mor F, Ozmen O - Toxins (Basel) (2015)

Kidney perfusion efficiency in rats receiving dietary ochratoxin A; contrasting sections stained with haematoxylin and eosin. (A) Not perfused; medullary blood vessels filled with erythrocytes (arrows); (B) Moderately efficient perfusion; numerous erythrocytes (arrows) in the medullary blood vessels; (C) Efficiently perfused kidney, no erythrocytes in the cortical blood vessels and glomeruli; (D) Efficiently perfused kidney; medullary blood vessels empty. Bar = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4417951&req=5

toxins-07-01005-f001: Kidney perfusion efficiency in rats receiving dietary ochratoxin A; contrasting sections stained with haematoxylin and eosin. (A) Not perfused; medullary blood vessels filled with erythrocytes (arrows); (B) Moderately efficient perfusion; numerous erythrocytes (arrows) in the medullary blood vessels; (C) Efficiently perfused kidney, no erythrocytes in the cortical blood vessels and glomeruli; (D) Efficiently perfused kidney; medullary blood vessels empty. Bar = 100 μm.
Mentions: The study focuses on the situation within individuals and therefore tabulated findings (Table 1) show both individual data and gender group means where relevant. Generally, the measured OTA values in plasma were seven- to eight-fold higher than those in the normal (non-perfused) kidney. Qualitative monitoring of technical efficiency of flushing blood from the renal vasculature (Figure 1), assessed by histology of a small portion of each perfused kidney, clearly demonstrated the degree of success according to the reduction in the erythrocyte population that is naturally abundant in non-perfused kidney (Figure 1A). There was consistent correlation between the degree of perfusion efficiency predicted from histology (Figure 1B–D) and the percent efficiency values calculated from subsequent measurement of OTA in the perfused organs are described below (Table 1).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Environmental Policy, Imperial College London, London SW7 2AZ, UK. p.mantle@imperial.ac.uk.

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.

Show MeSH
Related in: MedlinePlus