Oral and intraperitoneal acute toxicity studies of yessotoxin and homoyessotoxins in mice

A. Tubaro, S. Sosa, M. Carbonatto, G. Altinier, F. Vita, M. Melato, M. Satake, T. Yasumoto

Research output: Contribution to journalArticlepeer-review

Abstract

The acute toxicity of yessotoxin (YTX), homoyessotoxin (homoYTX) and 45-hydroxy-homoyessotoxin (45-OH-homoYTX) has been studied in comparison to that of okadaic acid (OA), the main diarrhogenic toxin, both after intraperitoneal (i.p.) and oral administration. After i.p. administration, homoYTX and YTX showed similar lethality (LD50=444 μg/kg and 512 μg/kg), higher than that of OA (LD50=225 μg/kg), while 750 μg/kg of 45-OH-homoYTX did not cause death. OA induced the already known toxic signs: before death, mice were motionless and cyanotic; small intestine and liver damage were shown at post-mortem. Mice treated with YTX and homoYTX were restless and jumped before death; necroscopy did not show major changes. After oral treatment, 2 mg/kg of OA induced diarrhoea and body weight loss, causing 4/5 deaths; necroscopy and/or histology revealed degenerative lesions to small intestine, forestomach and liver (confirmed by increased plasma transaminase), but no myocardium alterations. On the contrary, the oral treatment with YTX (1 and 2 mg/kg) and its derivatives (1 mg/kg) did not cause any death or signs of toxicity, except some ultrastructural myocardiocyte alterations, adjacent to capillaries, such as cytoplasmic protrusions (YTX, 1 and 2 mg/kg), fibrillar alteration (YTX, 1 mg/kg) or mitochondria assemblage (45-OH-homoYTX). Altogether, our data show that YTX and its derivatives are less toxic than OA after acute oral and i.p. treatments, at doses which may represent up to 100 times of the possible human daily intake.

Original languageEnglish
Pages (from-to)783-792
Number of pages10
JournalToxicon
Volume41
Issue number7
DOIs
Publication statusPublished - Jun 1 2003

Keywords

  • 45-hydroxy-homoyessotoxin
  • Acute toxicity
  • Homoyessotoxin
  • Intraperitoneal administration
  • Mice
  • Okadaic acid
  • Oral administration
  • Yessotoxin

ASJC Scopus subject areas

  • Toxicology

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