13-Desmethyl spirolide-c and 13,19-didesmethyl spirolide-c trans-epithelial permeabilities: Human intestinal permeability modelling.
Summary of "13-Desmethyl spirolide-c and 13,19-didesmethyl spirolide-c trans-epithelial permeabilities: Human intestinal permeability modelling."
Human intestinal permeability prediction is an increasingly important field that helps to explain how efficient the absorption of drugs is. Spirolides, cyclic imines produced by dinoflagellates from the genera Alexandrium, can be accumulated in mollusks usually consumed by humans. These compounds exert neurological symptoms when injected intra-peritoneally in mice, although they seem to be less toxic by oral administration. In this study, we evaluate two of the most abundant analogues, 13-desmethyl spirolide C and 13,19-didesmethyl spirolide C and their ability to cross the human intestinal epithelium by the use of Caco-2 trans-epithelial permeability assays as a model. Toxin quantifications were carried out by using the liquid chromatography-tandem mass spectrometry analytical technique. We found that both compounds cross the Caco-2 epithelial barrier without altering the trans-epithelial electric resistance of the monolayer. The apparent permeability (P(app)) coefficient calculated was 18.65±1.2×10(-6)cm/s for 13-desmethyl spirolide C while a little lesser, 12.32±3.18×10(-6)cm/s, for 13,19-didesmethyl spirolide C. P(app) coefficients allow us to predict a human intestinal permeability ≥80% and ≥50%, respectively for each compound. Those results demonstrate that spirolides would be highly absorbed in the human intestine, thus being able to enter the circulatory system and to reach different organs where they could be accumulated or exert an unpredictable effect. Thus, it is necessary to carry out new studies about their pharmacokinetics and evaluate their potential acute and/or chronic effect on the human body.
Departamento de Farmacología, Facultad de Veterinaria, Campus de Lugo, Universidad de Santiago de Compostela, 27002 Lugo, Spain.
This article was published in the following journal.
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21689715
- DOI: http://dx.doi.org/10.1016/j.tox.2011.06.003
Medical and Biotech [MESH] Definitions
Gene Products, Tax
Transcriptional trans-acting proteins of the promoter elements found in the long terminal repeats (LTR) of HUMAN T-LYMPHOTROPIC VIRUS 1 and HUMAN T-LYMPHOTROPIC VIRUS 2. The tax (trans-activator x; x is undefined) proteins act by binding to enhancer elements in the LTR.
The joining of RNA from two different genes. One type of trans-splicing is the "spliced leader" type (primarily found in protozoans such as trypanosomes and in lower invertebrates such as nematodes) which results in the addition of a capped, noncoding, spliced leader sequence to the 5' end of mRNAs. Another type of trans-splicing is the "discontinuous group II introns" type (found in plant/algal chloroplasts and plant mitochondria) which results in the joining of two independently transcribed coding sequences. Both are mechanistically similar to conventional nuclear pre-mRNA cis-splicing. Mammalian cells are also capable of trans-splicing.
DNA sequences that form the coding region for the protein responsible for trans-activation of transcription (tat) in human immunodeficiency virus (HIV).
A member of the P450 superfamily, this enzyme catalyzes the first oxidative step of the phenylpropanoid pathway in higher PLANTS by transforming trans-cinnamate into p-coumarate.
An enzyme that catalyzes the synthesis of geranylgeranyl diphosphate from trans, trans-farnesyl diphosphate and isopentenyl diphosphate.
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