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Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats

Deman Najar1, Börje Haraldsson2, Annika Thorsell3

  • 1Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden. deman.najar@neuro.gu.se.

Toxins
|August 22, 2018
PubMed

Insights

Orellanine, a mushroom toxin, concentrates in kidneys. Its elimination primarily occurs through glomerular filtration and peritoneal dialysis, suggesting potential therapeutic applications.

Area of Science:

  • Toxicology
  • Pharmacokinetics
  • Nephrology

Background:

  • Orellanine, a nephrotoxin from Cortinarius mushrooms, targets proximal tubular cells.
  • Potential therapeutic use in metastatic renal cancer due to cell specificity.
  • Limited understanding of orellanine's distribution and elimination hinders therapeutic development.

Purpose of the Study:

  • To investigate the distribution and pharmacokinetic properties of orellanine in rats.
  • To determine orellanine elimination pathways, including glomerular filtration and peritoneal dialysis.

Main Methods:

  • Intravenous injection of unlabeled and ³H-labeled orellanine (5 mg/kg) in Wistar and Sprague Dawley rats.
  • Distribution analysis using radioluminography.
  • Pharmacokinetic analysis via LC-MS/MS and β-scintillation in control and renal artery-ligated rats, with and without peritoneal dialysis.

Main Results:

  • Highest orellanine concentrations detected in kidney cortex and bladder.
  • Orellanine half-life: 109 ± 6 min in controls.
  • Half-life significantly increased in renal artery-ligated rats (756 ± 98 min without dialysis, 238 ± 28 min with dialysis).

Conclusions:

  • Orellanine is primarily eliminated via glomerular filtration.
  • Peritoneal dialysis effectively enhances orellanine elimination.
  • Findings support further research into orellanine's therapeutic potential for renal cell carcinoma.
Keywords:
clearancefungal toxinhalf-lifeorellanine

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