Toxicity of yessotoxin in experiment in vivo
O.V. Bagryantseva1,2, I.V. Gmoshinskii1, A.D. Evstratova1, E.N. Trushina1, O.K. Mustafina1, Kh.S. Soto1, V.A. Shipelin1, A.A. Shumakova1, A.D. Panova2, S.A. Khotimchenko1,2
1Federal Research Center for Nutrition, Biotechnology and Food Safety, 2/14 Ust'inskiy lane, Moscow, 109240, Russian Federation
2I.M. Sechenov First Moscow State Medical University, 8 Trubetskaya Str., build. 2, Moscow, 119991, RussianFederation
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.
- Paz В., Daranas А.Н., Norte М., Riobó P., Franco J.M., Fernández J.J. Yessotoxins, a Group of Marine Polyether Tox-ins: an Overview. Mar. Drugs., 2008, vol. 6, pp. 73–102. DOI: 10.3390/md20080005
- Alfonso A., de la Rosa L., Vieytes M.R., Yasumoto T., Botana L.M.Yessotoxin, a novel phycotoxin, activates phos-phodiesterase activity. Effect of yessotoxin on cAMP levels in human lymphocytes. Biochem. Pharmacol., 2003, vol. 65, no. 2, pp. 193–208.
- Report of the Joint FAO/IOC/WHO ad hoc Expert Consultation on Biotoxins in Bivalve Molluscs. Oslo, Norway,
26–30 September 2004. Short Summary.UNESCO, 2005, 8 p. Available at:http://unesdoc.unesco.org/images/0013/001394/139421e.pdf (16.04.2018). - Malagoli D., Ottaviani E. Yessotoxin affects fMLP-induced cell shape changes in Mytilusgalloprovincialis immunocytes. Cell. Biol. Int., 2004, vol. 28, no.1, pp. 57–61.
- Alfonso A., Vieytes M.R., Botana L.M. Yessotoxin, a Promising Therapeutic Tool. Mar. Drugs., 2016, vol. 14, pp. 30. DOI: 10.3390/md14020030
- Marine biotoxins in shellfish – Yessotoxin group. Scientific Opinion of the Panel on Contaminants in the Food chain (Question No EFSA-Q-2006-065D). The EFSA Journal, 2008, vol. 907, pp. 1–62. Available at: http://www.efsa.euro-pa.eu/sites/default/files/scientific_output/files/m... (16.04.2018).
- Franchini A., Malagoli D., Ottaviani E. Targets and Effects of Yessotoxin, Okadaic Acid and Palytoxin: A Differential Review. Mar. Drugs., 2010, vol. 8, pp. 658–677. DOI: 10.3390/md8030658
- Korsnes M.S Apoptotic events by yessotoxin in myoblast cell lines from rat and mouse. Toxicol. in vitro, 2006, vol. 20, pp. 1077–1087.
- Korsnes M.S., Korsnes R. Mitotic Catastrophe in BC3H1 Cells following Yessotoxin Exposure. Front. Cell. Dev. Biol., 2017, vol. 5, no. 30, 18 p. DOI: 10.3389/fcell.2017.00030
- Marine biotoxins. Food and Nutrition Paper (80). Rome: Food and agriculture organization of the united nations, 2004, 287 p.
- Regulation (EC) No 853/2004 of the European Parliament and of the Council of 29 April 2004. Official Journal of the European Union, 2004. Available at: https://eur-lex.europa.eu/LexUriServ/LexUri-Serv.do?uri=OJ:L:2004:139:00... (16.04.2018).
- Commission Regulation (EU) No 786/2013 of 16 August 2013 amending Annex III to Regulation (EC) No 853/2004 of the European Parliament and of the Council as regards the permitted limits of yessotoxins in live bivalve mollusks. Official Journal of the European Union, 2013. Available at: https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2013:220:
0014:0014:EN:PDF (16.04.2018). - Ohkawa H., Ohishi N., Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 1979, vol. 95, no. 2, pp. 351–358.
- Razygraev A.V. Metod opredeleniya glutationperoksidaznoiaktivnosti s ispol'zovaniemperoksidavodoroda i 5,5'-ditiobis(2-nitrobenzoinoi kisloty) [A procedure for determining glutathione peroxidase activity with hydrogen peroxide and 5 5'-dithiobis(2-nitrobenzoic acid)]. Kliniko-laboratornyikonsilium, 2004, no. 4, pp. 19–22 (in Russian).
- Raspopov R.V., Trushina E.N., Gmoshinsky I.V., Khotimchenko S.A. Biodostupnost' nanochastitsoksida-zhelezapriispol'zovaniiikhvpitanii. Rezul'taty eksperimentov na krysakh [Bioavailability of nanoparticles of ferric oxide when used in nutrition. Experimental results in rats]. Voprosypitaniya, 2011, vol. 80, no. 3, pp. 25–30 (in Russian).
fcrisk.ru
