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Assessment of the chemopreventive effect of casearin B, a clerodane diterpene extracted from Casearia sylvestris (Salicaceae).

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (2012-12-04)
Aline M Prieto, André G dos Santos, Ana Paula S Oliveira, Alberto J Cavalheiro, Dulce H S Silva, Vanderlan S Bolzani, Eliana Ap Varanda, Christiane P Soares
RÉSUMÉ

Studies have shown that Casearia sylvestris compounds protect DNA from damage both in vitro and in vivo. Complementarily, the aim of the present study was to assess the chemopreventive effect of casearin B (CASB) against DNA damage using the Ames test, the comet assay and the DCFDA antioxidant assay. The genotoxicity was assessed by the comet assay in HepG2 cells. CASB was genotoxic at concentrations higher than 0.30 μM when incubated with the FPG (formamidopyrimidine-DNA glycosylase) enzyme. For the antigenotoxicity comet assay, CASB protected the DNA from damage caused by H(2)O(2) in the HepG2 cell line in concentrations above 0.04 μM with post-treatment, and above 0.08 μM with pre-treatment. CASB was not mutagenic (Ames test) in TA 98 and TA 102. In the antimutagenicity assays, the compound was a strong inhibitor against aflatoxin B1 (AFB) in TA 98 (>88.8%), whereas it was moderate (42.7-59.4%) inhibitor against mytomicin C (MMC) in TA 102. Additionally, in the antioxidant assay using DCFDA, CASB reduced reactive oxygen species (ROS) generated by H(2)O(2). In conclusion, CASB was genotoxic to HepG2 cells at high concentrations; was protective of DNA at low concentrations, as shown by the Ames test and comet assay; and was also antioxidant.

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Sigma-Aldrich
Aflatoxin B1 from Aspergillus flavus, from Aspergillus flavus
Supelco
Aflatoxin B1 solution, 2 μg/mL in acetonitrile, analytical standard
Supelco
Aflatoxin B1 solution, 3 μg/mL in benzene:acetonitrile (98:2), analytical standard