TY - JOUR
T1 - Oral and intraperitoneal acute toxicity studies of yessotoxin and homoyessotoxins in mice
AU - Tubaro, A.
AU - Sosa, S.
AU - Carbonatto, M.
AU - Altinier, G.
AU - Vita, F.
AU - Melato, M.
AU - Satake, M.
AU - Yasumoto, T.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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.
AB - 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.
KW - 45-hydroxy-homoyessotoxin
KW - Acute toxicity
KW - Homoyessotoxin
KW - Intraperitoneal administration
KW - Mice
KW - Okadaic acid
KW - Oral administration
KW - Yessotoxin
UR - http://www.scopus.com/inward/record.url?scp=0038019996&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038019996&partnerID=8YFLogxK
U2 - 10.1016/S0041-0101(03)00032-1
DO - 10.1016/S0041-0101(03)00032-1
M3 - Article
C2 - 12782078
AN - SCOPUS:0038019996
VL - 41
SP - 783
EP - 792
JO - Toxicon
JF - Toxicon
SN - 0041-0101
IS - 7
ER -