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Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats

Journal article
Authors Deman Hadi Najar
Börje Haraldsson
Annika Thorsell
Carina Sihlbom
Jenny Nyström
Kerstin Ebefors
Published in Toxins
Volume 10
Issue 8
ISSN 2072-6651
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Physiology
Core Facilities, Proteomics
Language en
Links dx.doi.org/10.3390/toxins10080333
Keywords orellanine, clearance, fungal toxin, half-life, renal-cell carcinoma, cortinarius-orellanus, mushroom nephrotoxin, fungal toxin, cancer, fries, anesthesia, ingestion, radicals, kidney, Food Science & Technology, Toxicology, lpech n, 1990, presse medicale, v19, p122, humacher t, 1983, archives of toxicology, v53, p87, ast h, 1988, archives of toxicology, v62, p89, hmlow ev, 1985, tetrahedron letters, v26, p4903
Subject categories Neurosciences

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 H-3-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 -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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