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Toxins 2018, 10(8), 333; https://doi.org/10.3390/toxins10080333

Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats

1
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden
2
Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden
*
Author to whom correspondence should be addressed.
Received: 6 July 2018 / Revised: 14 August 2018 / Accepted: 15 August 2018 / Published: 17 August 2018
(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)
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Abstract

Orellanine is a nephrotoxin found in mushrooms of the Cortinarius family. Accidental intake of this substance may cause renal failure. Orellanine is specific for proximal tubular cells and could, therefore, potentially be used as treatment for metastatic renal cancer, which originates from these cells. However, more information is needed about the distribution and elimination of orellanine from the body to understand its potential use for therapy. In this study, 5 mg/kg orellanine (unlabeled and 3H-labeled) was injected intravenously in rats (Wistar and Sprague Dawley). Distribution was measured (Wistar rats, n = 10, n = 12) using radioluminography and the highest amount of orellanine was found in the kidney cortex and bladder at all time-points investigated. The pharmacokinetic properties of orellanine was investigated using LC-MS/MS and β-scintillation to measure the amount of orellanine in plasma. Three groups of rats were investigated: control rats with intact kidneys (n = 10) and two groups with bilateral renal artery ligation (n = 7) where animals in one of these groups were treated with peritoneal dialysis (n = 8). Using LC-MS/MS, the half-life of orellanine was found to be 109 ± 6 min in the controls. In the groups with ligated renal arteries, orellanine had a half-life of 756 ± 98 min without and 238 ± 28 min with dialysis. Thus, orellanine was almost exclusively eliminated by glomerular filtration as well as by peritoneal dialysis. View Full-Text
Keywords: orellanine; clearance; fungal toxin; half-life orellanine; clearance; fungal toxin; half-life
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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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Najar, D.; Haraldsson, B.; Thorsell, A.; Sihlbom, C.; Nyström, J.; Ebefors, K. Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats. Toxins 2018, 10, 333.

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