Article ID Journal Published Year Pages File Type
5851642 Food and Chemical Toxicology 2013 8 Pages PDF
Abstract

(−)-Cubebin (CUB) is a lignan isolated from dry seeds of Piper cubeba. We aimed to assess its genotoxic potential and influence on chromosomal damage (frequency of micronuclei - MN) induced by doxorubicin (DXR) in V79 cells and by urethane (URE) in somatic Drosophila melanogaster cells. Our findings indicate an absence of a CUB-mediated genotoxic effect at the concentrations tested. The results also revealed that CUB significantly reduced the frequency of MN induced by DXR, with a mean reduction of 63.88%. In a previous study, our research group demonstrated an absence of CUB-mediated mutagenic effects through the wing Somatic Mutation and Recombination Test (SMART) in Drosophila. In the present study, we used the standard and high bioactivation versions of the SMART to estimate the antigenotoxic effects of CUB associated with URE. At lower concentrations, the recombination level decreased, but at the highest concentration, the recombination level increased. Our data and previous studies suggest that CUB may act as a free radical scavenger at low concentrations, a pro-oxidant at higher concentrations when it interacts with the enzymatic system that catalyzes the metabolic detoxification of DXR or URE, and/or an inducer of recombinational DNA repair.

Graphical abstract(1) http://upload.wikimedia.org/wikipedia/commons/thumb/f/f8/Piper_cubeba_-_K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-244.jpg/220px-Piper_cubeba_-_K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-244.jpg. (2) http://www.gourmetsleuth.com/images/cubeb_pepper.jpg. (3) Food Chem Toxicol, vol. 49, no. 6, pp. 1235-1241, 2011. (4) Mol Cell Biochem, v.207, n.1-2, Apr, p.77-86, 2000. (5) Adapted from: http://www.nature.com/nrg/journal/v2/n11/images/nrg1101-879a-f1.gif. (6) http://www.utm.utoronto.ca/∼w3mfitz/3rd%20instar.jpg. (7) http://0.tqn.com/d/chemistry/1/0/L/R/1/Urethane.jpg. (8) http://upload.wikimedia.org/wikipedia/commons/e/e7/Wing_D_suzukii_female.jpgDownload full-size imageHighlights► (−)-Cubebin CUB is not aneugenic or clastogenic in V79 cells. ► CUB, may act either as a free radical scavenger at low concentrations or as a pro-oxidant at higher concentrations. ► CUB may interact with the metabolic activation of URE. ► CUB associated with URE changes the mutational and recombinational frequencies in a concentration-dependent manner..

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