An in vitro comparison of the cytotoxic potential of selected dehydropyrrolizidine alkaloids and some N-oxides
| Autor: | Bryan L. Stegelmeier, Ammon W. Brown, Steven M. Colegate, Benedict T. Green, Reuel A. Field |
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| Rok vydání: | 2015 |
| Předmět: |
Pyrrolizidine alkaloid
Cell Survival Tetrazolium Salts Pilot Projects In Vitro Techniques Biology Pharmacology Toxicology Cyclic N-Oxides chemistry.chemical_compound Cell Line Tumor Lactate dehydrogenase Animals Humans Cytotoxic T cell Viability assay Cytotoxicity Pyrrolizidine Alkaloids Carcinogen Monocrotaline Molecular Structure Cytotoxins Riddelliine Hep G2 Cells Thiazoles HEK293 Cells chemistry Cattle Chickens Senecionine |
| Zdroj: | Toxicon. 97:36-45 |
| ISSN: | 0041-0101 |
| DOI: | 10.1016/j.toxicon.2015.02.001 |
| Popis: | Plants producing dehydropyrrolizidine alkaloids (DHPAs) are found throughout the world and they are dangerous to human and animal health. Several DHPAs are carcinogenic but only riddelliine has been classified as a potential human carcinogen by the National Toxicology Program. As DHPA-related carcinogenicity is probably linked to cytotoxicity, a model of CRL-2118 chicken hepatocyte cytotoxicity was developed to compare equimolar DHPA exposures between 19 and 300 μM. Alkaloid-related cytotoxicity was estimated using cytomorphology, cell viability reflected by mitochondrial function and cellular degeneration reflected by media lactate dehydrogenase activity. Lasiocarpine induced cytotoxicity and decreased cell viability in a concentration dependent manner at 24 h. At similar concentrations and exposures of 48 and 72 h, seneciphylline, senecionine, monocrotaline and riddelliine were cytotoxic. None of the DHPA-N-oxides were significantly cytotoxic at these concentrations. Using graphic analyses the median cytotoxic concentration (DHPA concentration that produced ½ the maximum response) were estimated. The estimated descending order of cytotoxicity was lasiocarpine, seneciphylline, senecionine, heliotrine, riddelliine, monocrotaline, riddelliine-N-oxide, lycopsamine, intermedine, lasiocarpine-N-oxide and senecionine-N-oxide. This comparison identifies DHPAs that were more cytotoxic than carcinogenic riddelliine. Additional studies to better characterize the carcinogenic potential of these alkaloids are essential to better determine the risk they each may pose for human and animal health. |
| Databáze: | OpenAIRE |
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