Toxicity of yessotoxin in experiment in vivo
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01.01.2018 |
Bagryantseva O.
Gmoshinskii I.
Evstratova A.
Trushina E.
Mustafina O.
Soto K.
Shipelin V.
Shumakova A.
Panova A.
Khotimchenko S.
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Health Risk Analysis |
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© 2013-2018 Federal Scientific Center for Medical and Preventive Health Risk Management Technologies. Yessotoxin (YTX) is a polyether. There are more than 90 known derivatives of yessotoxin. YTX was excluded from diarrhea toxins group as it, unlike okadaic acid, doesn't cause diarrhea. YTX chemical structure is similar to that of brevetoxins and ciguatoxins that influence functioning of calcium-sodium pump and trans-membrane ion channels. So, YTX can exert influence on functioning of all the organs and systems in a body. YTX is known to promote apoptosis in the cerebral tissues. Average lethal dose LD50 for YTX and its analogues varied from 100 μg/kg to 500-750 μg/kg; the figures were obtained in various experiments performed on mice. Safe YTX level for acute impact (acute reference dose) amounts to 25 μM/kg of body weight. Nowadays toxicity parameters for YTX and some of its analogues are determined; its basic action mechanisms and a role it plays in promoting apoptosis are well-known. In spite of more and more data on biological effects produced by YTX on a warm-blooded organism, experts are still unable to describe its action mechanisms precisely. Our research goal was to examine YTX toxicity in experiments in vivo in doses that were lower than the detected acute reference dose. The experiment was performed on 72 male Wistar rats with initial body weight being equal to 100±10 g. Animals were given dry balanced feedstuffproduced by "Laboratortakorm" LLC (Russia) and had free access to it. We used YTX preparation produced by "National Research Council Canada" (Canada) in our experiment; the preparation was a methanol solution (YTX content was equal to 4.3 μmol). We determined mass of internal organs, biochemical and hematological blood parameters, apoptosis of brain cells, malonic dialdehyde level in the brain and reduced glutathione in the liver. We showed that YTX doses (2μM/kg, 8μM/kg and 12μM/kg) lower than ARfD=2μM/kg can exert toxic impacts on a warm-blooded organism. The obtain data prove it is necessary to additionally assess risks of an increase in maximum permissible YTX contents in shellfish from 1 mg/kg to 3.75 mg/kg.
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Yessotoxin: Risk assessment for public health. Justification of regulations of content in seafood
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01.01.2018 |
Bagryantseva O.
Evstratova A.
Khotimchenko S.
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Voprosy Pitaniia |
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© 2018 GEOTAR-Media Publishing Group. Yessotoxin and its derivatives (about 90) are isolated from algae belonging to the species Protoceratium reticulatum, Gonyaulax cf. Spinifera, Lingulodinium polyedrum and from invertebrate organisms that feed on these algae. Previously yessotoxin have been associated with the group of diarrheal toxins. Later studies of the possible impact of yessotoxin on the activity of alkaline phosphatase allowed to exclude them from this group. Yessotoxin causes a violation of calcium entry in the cells, which, in turn, effects the calcium-calmodulin system and thus influences into homeostasis of the organism as a whole. It was shown that yessotoxin induces a biphasic change in the concentration of adenosine monophosphate, an initial increase with a subsequent relative decrease, within some minutes after adding the toxin to the lymphocytes cell culture. Yessotoxin has effects on immune system; which is manifested in an increase of cytokines level, by inducing the expression of the genes encoding them. Yessotoxin have impact into processes of cell adhesion via E-cadherin and, thus, could be an important factor in the development of Alzheimer's disease. It has been established that yessotoxin caused the development of apoptosis. In those cases all three mechanisms of cell death took place - apoptosis, paraptosis and autophagy. Yessotoxin's acute toxicity doses according to different data are from 100 to 500-750 μg per 1kg of body weight. Yessotoxin's acute reference dose (ARfD) - 25 μg/kg of body weight per day. The results of the analysis of yessotoxin level in shellfish meat showed that none of the studied samples contained more than 3.75 mg yessotoxin equivalents/kg shellfish meat. This level has been adopted by the European Union as the maximum acceptable level of yessotoxin in shellfish meat (EU Regulation N 786/2013). Presented data on the mechanism of action, toxicity and prevalence of yessotoxins make it necessary to establish regulations of their content in seafood, placed on the markets of the Eurasian Economic Union.
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