Disease relevance of Orellanine

• Orellanine, (2,2'-bipyridine)-3,3',4,4'-tetrol-1,1'-dioxide, the toxin from several Cortinariace species, induces an acute renal failure which can be very severe or even irreversible and fatal [1].
• The similarity of the structures of the toxin and of bipyridinium herbicides such as methylviologen (paraquat) or the nephrotoxic diquat led other authors to presume a similar mechanism for orellanine toxicity [2].
• The tentative diagnosis of acute renal failure due to orellanine intoxication was confirmed by the histologic finding of an acute interstitial nephritis in a first renal biopsy one week after onset of anuria [3].
• BACKGROUND: Mushroom poisoning by some species of the Cortinarius (Agaricales) often lead to irreversible renal failure caused by the nephrotoxin orellanine [4].

High impact information on Orellanine

• Generation of oxygen radicals from iron complex of orellanine, a mushroom nephrotoxin; preliminary ESR and spin-trapping studies [5].
• The negative toxin test in this second renal biopsy is possibly explained by a wide variability of pharmacokinetics of orellanine [3].
• Direct addition of orellanine to a cell-free system of rabbit reticulocyte lysate does not produce any inhibition of protein synthesis [6].
• Orellanine inhibits protein synthesis in Madin-Darby canine kidney cells, in rat liver mitochondria, and in vitro: indication for its activation prior to in vitro inhibition [6].
• Pure orellanine extracted from the mushroom Cortinarius orellanus is highly toxic in mice both when given intraperitoneally (LD50 = 12.5 mg/kg) or per os (LD50 = 90 mg/kg) [2].

Chemical compound and disease context of Orellanine

• The actual toxicity of orellanine is quite different from the values calculated based upon the postulated bipyridine structure [7].

Biological context of Orellanine

• A quantitative structure-activity relationship study on substituted pyridines as a contribution to the knowledge of the toxic effects of orellanine, a toxin from the mushroom Cortinarius orellanus [7].

Anatomical context of Orellanine

• However, no effect was observed on thylakoids (class C chloroplasts), showing that orellanine does not interfere with the chloroplastic electron transfer chain and that orellanine does not act like methylviologen (paraquat) in green plants, as previously suggested [8].
• Orellanine specifically inhibited alkaline phosphatase activity in LLC-PK1 renal epithelial cell cultures and in the colon carcinoma cell line Caco-2 without affecting gamma-glutamyl transpeptidase activity [9].

Associations of Orellanine with other chemical compounds

• An electrochemical study of orellanine and related compounds showed that orellanine can neither be reduced by electrons derived from H2O nor from NADPH, as is methylviologen in plant and animal cells, respectively [8].
• The present study demonstrates that the fluorescence is mainly due to ergosta-4,6,8(14),22-tetraen-3-one (8) and to photodecomposition products of the nephrotoxin orellanine (1) [10].
• Orellanine causes disruption of confluent monolayers and decreases the activities of membrane bound alkaline phosphatase and of cytosolic lactate dehydrogenase [11].

Gene context of Orellanine

• The efficiency of the haemoperfusion materials activated charcoal (DHP-1) and Amberlite XAD 4 resin at removing orellanine from plasma was tested in an in vitro model [12].

Analytical, diagnostic and therapeutic context of Orellanine

• Novel methods for identification and quantification of the mushroom nephrotoxin orellanine. Thin-layer chromatography and electrophoresis screening of mushrooms with electron spin resonance determination of the toxin [1].
• Peroxidase-mediated oxidation, a possible pathway for activation of the fungal nephrotoxin orellanine and related compounds. ESR and spin-trapping studies [13].
• Investigations on the mode of action of the fungus toxin orellanine on renal cell cultures [11].

References