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Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats

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 cel...

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Autores principales: Najar, Deman, Haraldsson, Börje, Thorsell, Annika, Sihlbom, Carina, Nyström, Jenny, Ebefors, Kerstin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116018/
https://www.ncbi.nlm.nih.gov/pubmed/30126099
http://dx.doi.org/10.3390/toxins10080333
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author Najar, Deman
Haraldsson, Börje
Thorsell, Annika
Sihlbom, Carina
Nyström, Jenny
Ebefors, Kerstin
author_facet Najar, Deman
Haraldsson, Börje
Thorsell, Annika
Sihlbom, Carina
Nyström, Jenny
Ebefors, Kerstin
author_sort Najar, Deman
collection PubMed
description 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 (3)H-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 were 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.
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spelling pubmed-61160182018-08-31 Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats Najar, Deman Haraldsson, Börje Thorsell, Annika Sihlbom, Carina Nyström, Jenny Ebefors, Kerstin Toxins (Basel) Article 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 (3)H-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 were 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. MDPI 2018-08-17 /pmc/articles/PMC6116018/ /pubmed/30126099 http://dx.doi.org/10.3390/toxins10080333 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Najar, Deman
Haraldsson, Börje
Thorsell, Annika
Sihlbom, Carina
Nyström, Jenny
Ebefors, Kerstin
Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats
title Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats
title_full Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats
title_fullStr Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats
title_full_unstemmed Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats
title_short Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats
title_sort pharmacokinetic properties of the nephrotoxin orellanine in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116018/
https://www.ncbi.nlm.nih.gov/pubmed/30126099
http://dx.doi.org/10.3390/toxins10080333
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