Early morphological and functional alterations in canine hepatocytes due to α-amanitin, a major toxin of Amanita phalloides
Jan Magdalan , Alina Ostrowska , Marzena Podhorska-Okołów , Aleksandra Piotrowska , Ilona Iżykowska , Marcin Nowak , Barbara Dolińska-Krajewska , Maciej Zabel , Adam Szeląg , Piotr Dzięgiel
AbstractThe toadstool death cap (Amanita phalloides) and its subspecies, destroying angel (A. virosa) and death angel (A. verna) are responsible for nearly 95% of all fatal mushroom poisonings. High mortality rate in A. phalloides intoxications is principally a result of the acute liver failure following significant hepatocyte damage due to hepatocellular uptake of amanitins, the major toxins of this mushroom. This study evaluated early morphological and functional alterations in hepatocytes exposed to different concentrations of α-amanitin (α-AMA). All experiments were performed on cultured canine hepatocytes since intoxicated with A. phalloides dogs have clinical course and pathological findings similar to those seen in humans. The overall functional integrity and viability of cultured hepatocytes were assessed using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and by measurements of lactate dehydrogenase (LDH), total protein, and urea levels. Our results showed that the course of α-AMA toxicity in cultured dog hepatocytes is divided into two phases. The first phase comprises functional cell impairments expressed by significant increase of LDH activity and inhibition of protein and urea synthesis when compared with the control group. This is followed by discrete changes in hepatocyte ultrastructure, including marginalization and condensation of nuclear chromatin, as well as formation of the foamlike cytoplasm. The second stage is lethal and is characterized by ongoing necrosis, and/or apoptosis. This may be related to dose of toxin and time of exposure.
|Journal series||Archives of Toxicology, ISSN 0340-5761, e-ISSN 1432-0738, (A 30 pkt)|
|Publication size in sheets||0.5|
|Keywords in English||Amanita phalloides; Amanitin; Canine hepatocytes; Intoxication|
|ASJC Classification||; ;|
|Publication indicators||= 19; = 18; : 2009 = 0.999; : 2009 = 3.312 (2) - 2009=2.626 (5)|
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