Aflatoxin B1
From ToxBankWiki
Executive Summary
Compound | Aflatoxin B1 |
Toxicities | Apoptosis |
Mechanisms | Aflatoxin is metabolized to a reactive epoxide that forms adducts with DNA and protein lysine groups. The epoxide is hydrolyzed to a dialdehyde, which also forms adducts with protein lysine groups. Because mitochondrial energy production is not significantly disrupted by this toxin, ATP levels are maintained and cellular damage triggers apoptosis rather than necrosis. It is not clear, however, which specific biological adduct(s) trigger apoptosis. |
Comments | This compound was selected as standard to exemplify the chemistry of reactive epoxides and lysine reagents. Carcinogenic effects that are observed on long-term, low-dose exposure are of less interest in these studies.
CAUTION: Aflatoxin is extremely toxic. Long-term exposure to sub-microgram levels can cause cancer. Handle the solid compound with extreme care, and handle the compound in solution when possible. Not recommended for high-throughput screening assays. |
Feedback Contact | Gold Compound Working Group (GCWG) |
Aflatoxin B1 | |
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Identifiers | |
Leadscope Id | LS-584 |
CAS | 1162-65-8 |
ChemSpider | 162470 |
ChEBI | 2504 |
Pathway DBs | |
KEGG | C06800 |
Assay DBs | |
PubChem CID | 186907 |
Omics DBs | |
Properties | |
ToxCast Accepted | no |
Toxic Effect | Apoptosis |
ToxBank Accepted | yes |
Approved on | 2011-06-28 |
Target | possibly DNA binding |
Toxicities | Apoptosis |
- In Vivo Data
- LIINTOP Data
- PK-ADME Data
- 'Omics and IC50 Data
- Physical Properties
- Recommended Product and Source
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PubMed references
The following resource link will perform a PubMed query for the terms "Aflatoxin B1" and "liver toxicity".
Aflatoxin B1 Search
EPA Summary
The table listed below contains a summarized listing of toxic effect information leveraged from the 6th European Framework Programme project LIINTOP. For a complete listing of the Gold Compound evaluation criteria please see the Gold Compound Evaluation and Comments immediately following the summary table below.
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Summary Hepatotoxic Effects from the LIINTOP FP6 Program | |||||||||||||||||||||
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[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] |
References
- ↑ Li, A.P., 2002. A review of the common properties of drugs with idiosyncratic hepatotoxicity and the ‘‘multiple determinant hypothesis” for the manifestation of idiosyncratic drug toxicity. Chem. Biol. Interact. 142, 7–23. doi:10.1016/S0009-2797(02)00051-0
- ↑ Feldmann, G., 2006. Liver apoptosis. Gastroenterol. Clin. Biol. 30, 533–545.
- ↑ Gomez-Lechon, M.J., O’Connor, E., Castell, J.V., Jover, R., 2002. Sensitive markers used to identify compounds that trigger apoptosis in cultured hepatocytes. Toxicol. Sci. 65, 299–308. doi:10.1093/toxsci/65.2.299
- ↑ Gomez-Lechon, M.J., O’Connor, J.E., Lahoz, A., Castell, J.V., Donato, M.T., 2008. Identification of apoptotic drugs: multiparametric evaluation in cultured hepatocytes. Curr. Med. Chem. 15, 2071–2085. pmid:18691057
- ↑ Gomez-Lechon, M.J., Ponsoda, X., O’Connor, E., Donato, T., Jover, R., Castell, J.V., 2003. Diclofenac induces apoptosis in hepatocytes. Toxicol. in Vitro 17, 675– 680. doi:10.1016/S0887-2333(03)00105-X
- ↑ Kass, G.E., Macanas-Pirard, P., Lee, P.C., Hinton, R.H., 2003. The role of apoptosis in acetaminophen-induced injury. Ann. NY Acad. Sci. 1010, 557–559. doi:10.1196/annals.1299.103
- ↑ Ioannides, C., Lewis, D.F., 2004. Cytochromes P450 in the bioactivation of chemicals. Curr. Top. Med. Chem. 4, 1767–1788. doi:10.2174/1568026043387188
- ↑ Kang, P., Dalvie, D., Smith, E., Zhou, S., Deese, A., Nieman, J.A., 2008. Bioactivation of flutamide metabolites by human liver microsomes. Drug Metab. Dispos. 36, 1425–1437. doi:10.1124/dmd.108.020370
- ↑ Li, A.P., 2002. A review of the common properties of drugs with idiosyncratic hepatotoxicity and the ‘‘multiple determinant hypothesis” for the manifestation of idiosyncratic drug toxicity. Chem. Biol. Interact. 142, 7–23.doi:10.1016/S0009-2797(02)00051-0
- ↑ Park, K., Williams, D.P., Naisbitt, D.J., Kitteringham, N.R., Pirmohamed, M., 2005b. Investigation of toxic metabolites during drug development. Toxicol. Appl. Pharmacol. 207, 425–434. {{doi|10.1016/j.taap.2005.02.029
- ↑ Reddy, M.V., Storer, R.D., Laws, G.M., Armstrong, M.J., Barnum, J.E., Gara, J.P., McKnight, C.G., Skopek, T.R., Sina, J.F., DeLuca, J.G., Galloway, S.M., 2002. Genotoxicity of naturally occurring indole compounds: correlation between covalent DNA binding and other genotoxicity tests. Environ. Mol. Mutagen. 40, 1–17. doi:10.1002/em.10088
- ↑ Hynes, J., Marroquin, L.D., Ogurtsov, V.I., Christiansen, K.N., Stevens, G.J., Papkovsky, D.B., Will, Y., 2006. Investigation of drug-induced mitochondrial toxicity using fluorescence-based oxygen-sensitive probes. Toxicol. Sci. 92, 186–200. doi:10.1093/toxsci/kfj208
- ↑ Johannsen, D.L., Ravussin, E., 2009. The role of mitochondria in health and disease. Curr. Opin. Pharmacol. 9, 780–786. doi:10.1016/j.coph.2009.09.002
- ↑ Jones, D.P., Lemasters, J.J., Han, D., Boelsterli, U.A., Kaplowitz, N., 2010. Mechanisms of pathogenesis in drug hepatotoxicity putting the stress on mitochondria. Mol. Interv. 10, 98–111. doi:10.1124/mi.10.2.7
- ↑ Labbe, G., Pessayre, D., Fromenty, B., 2008. Drug-induced liver injury through mitochondrial dysfunction: mechanisms and detection during preclinical safety studies. Fundam. Clin. Pharmacol. 22, 335–353. doi:10.1111/j.1472-8206.2008.00608.x
- ↑ Masubuchi, Y., 2006. Metabolic and non-metabolic factors determining troglitazone hepatotoxicity: a review. Drug Metab. Pharmacokinet. 21, 347–356. doi:10.2133/dmpk.21.347
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Calculated/Predicted Properties
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