Oral toxicity of okadaic acid in mice: study of lethality, organ damage, distribution and effects on detoxifying gene expression.
In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produce lesions in liver, small intestine and forestomach. Because several reports differ in the damage detected in different organs, and on okadaic acid distribution after consumption, we determined the toxicity of this compound after oral administration to mice. After 24 hours, histopathological examination showed necrotic foci and lipid vacuoles in the livers of intoxicated animals. By immunohistochemical analysis, we detected this toxin in the liver and kidneys of intoxicated animals. Okadaic acid induces oxidative stress and can be activated in vitro into reactive compounds by the post-mitochondrial S9 fraction, so we studied the okadaic effect on the gene expression of antioxidant and phase II detoxifying enzymes in liver. We observed a downregulation in the expression of these enzymes and a reduction of protein expression of catalase and superoxide dismutase 1 in intoxicated animals.
Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain. Luis.Botana@usc.es.
Andres C
AC
Vieira
Juan A
JA
Rubiolo
Henar
H
López-Alonso
José Manuel
JM
Cifuentes
Amparo
A
Alfonso
Roberto
R
Bermúdez
Paz
P
Otero
Mercedes R
MR
Vieytes
Félix V
FV
Vega
Luis M
LM
Botana
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced; D005243:Feces / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D008658:Inactivation, Metabolic; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D019319:Okadaic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects / Q000473:pathology
D000975:Antioxidants; D019319:Okadaic Acid