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Orellanine is a hydroxylated bipyridyl-N,N-dioxide (Figure 3.2a), associated in the mushroom with the corresponding monoxide, orellinine (Figure 3.2b). Under UV light, orellanine and orellinine stepwise lose the N-oxides, leading to orelline (Figure 3.2c) as the stable, but non-toxic, end product. Orellinine is less toxic than orellanine, and there is evidence that the species with toxic activity is not orellanine itself but an oxidation product, the semiquinone (Figure 3.2d), produced in cells by a peroxidase reaction (Oubrahim, et al., 1998). The semiquinone is a radical that probably causes intracellular depletion of glutathione and ascorbate as the toxic event. Toxicity mainly develops in the

Figure 3.2 Structures of (a) orellanine, (b) orellinine, (c) orilline, and (d) the radical semiquinone of orellanine, suggested as the toxic species.

Figure 3.2 Structures of (a) orellanine, (b) orellinine, (c) orilline, and (d) the radical semiquinone of orellanine, suggested as the toxic species.

kidney, leading to renal failure. No toxic effects were found in the liver. On the molecular level, orellanine was shown to be an inhibitor of alkaline phosphatase (Ruedl et al., 1989).

3.3.3 Symptoms and Treatment

Symptoms of orellanine poisoning are typical of renal damage, developing two to four days, in some cases up to fourteen days, after the mushroom meal. During the latent period, patients have mild GI symptoms which may be overlooked. Accordingly, patients present themselves at hospital only at the stage when renal failure has developed. At that stage, patients suffer from abdominal or lumbar pain, headache, muscular pain, and fatigue, and present laboratory values showing leukocyturia, hematuria, and increased serum values of creatinine and potassium. Out of a group of 22 patients treated in Sweden in the years 1979 to 1993, nine patients developed chronic renal failure requiring dialysis or transplantation.

As with amatoxin poisoning, attempts to remove the toxin from plasma by extra-corporal purification methods at the time of hospitalization do not seem promising because of the long latent period. However, beside supportive care, hemodialysis is the option during the clinical course. For a recent review on Corinarius spp. poisoning, see Danel et al. (2001). A renal transplantation should not be carried out too early; the mean time for a transplant among the cases published so far was 6 to 30 months.

A method for estimating the prognosis in individual cases was recently proposed by Holmendahl; the Cortinarius Nephro Toxicity (CNT) Prognosis Index. This test is based on the serum creatinine level before treatment (y) and the number of days elapsed (X):

where CNT <1.1 indicates a good prognosis; CNT = 1.1-2.2 indicates a probable chronic failure; and CNT >2.1 suggests a poor outcome requiring renal replacement therapy (Persson and Karlson-Stiber, in press).

3.3.4 Detection

The toxins are easily detected, after separation of the compounds from plasma and renal tissue on silica thin layers, by their fluorescence in UV light: orellanine is visible as navy blue, orellinine as dark blue, and orelline as light blue (Horn et al., 1997). Beside thin-layer chromatography (TLC), use of HPLC for the analysis of orellanine, e.g., in mushroom extracts, has also been reported. Quantitative analysis of orellanine in plasma samples, or in (rat) urine samples, was performed by extraction of orellanine on XAD-4 resin, two-dimensional TLC on cellulose, and spectrophotometric evaluation of the orelline produced on the TLC plates after UV-induced decomposition of the orellanine.

3.4 gyrometrin

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