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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-15
pubmed:abstractText
The metabolism of toxins that have accumulated in fish and shellfish is considered a detoxification process, as happens with pectenotoxins (PTXs) in the Japanese scallop Patinopecten yessoensis. PTXs are macrolactones that display hepatotoxicity in mice, principally by capping or sequestering actin, their molecular target. PTX-2, which is considered to be the parental compound, oxidizes progressively to PTX-1, PTX-3, and PTX-6 in the Japanese scallop. In this study, we observed that PTX-1, PTX-6, and PTX-9 induce dose-dependent damage in the actin cytoskeleton and in the viability of primary cultured rat hepatocytes. In Clone 9 rat hepatocytes, PTX-1 and PTX-9 also affect the morphology of cells, but surprisingly, PTX-6 induced no effect. In accordance with this lack of activity, the actin cytoskeleton of CaCo-2 cells, another epithelial cell line, is not affected by PTX-6. In conclusion, the order of cytotoxicity of the analogues is PTX-2 > PTX-1 > PTX-6 >PTX-9. From a structure-activity perspective, the increase in the level of oxidation of the PTX molecule on C-43 decreases its cytotoxicity. Furthermore, PTX-6 is not able to induce effects on immortal cells while retaining its toxicity against primary cultured cells, whereas PTX-9, a 7-S-isomer, is active in both cellular models. The different cytotoxicities exerted by PTX-6 on cell lines and primary cells could be determined by the presence of a carboxylic acid group on C43 of the PTX molecule.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1520-5010
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
504-15
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Impact of the pectenotoxin C-43 oxidation degree on its cytotoxic effect on rat hepatocytes.
pubmed:affiliation
Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't