Toxicity of yessotoxin in experiment in vivo

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 г. Animals were given dry balanced feedstuff produced 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.