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 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

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

Publication and Content Type

ref (subject category)

art (subject category)