Screening of cytoprotectors against methotrexate-induced cytogenotoxicity from bioactive phytochemicals, by umu test combined with micronucleus Assay
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Abstract
To develop new cytoprotectors to reduce the risk of second cancers caused by methotrexate-induced cytogenotoxicity, cytoprotective effects of ten kinds of phytochemicals and their combinations were evaluated by umu test combined with micronucleus assay. It is demonstrated that allicin, proanthocyanidins, polyphenols, eleutherosides and isoflavones owned higher antimutagenic activities than other phytochemicals. At the highest dose tested, the MTX genetoxicity was inhibited by 34.03%~67.12%. Of all the bioactive phytochemical combinations, the combination of grape seed proanthocyanidins and eleutherosides from siberian ginseng as well as green tea polyphenols and eleutherosides showed stronger antimutagenic effects, the inhibition rate of methotrexate-induced genotoxicity separately reached 74.7 ± 6.5 % and 71.8 ± 4.7%. The Kunming mice treated by MTX along with bioactive phytochemicals combinations showed significant reduction in micronucleus induction and sperm abnormality rate compared to MTX treated control groups without cytoprotector candidates (p<0.01). Moreover, obvious increases in thymus and spleen indices were observed in cytoprotector candidates treated groups. The results indicated that bioactive phytochemicals combinations owned potentials to be used as new cytoprotectors, besides umu test was the same effective assay to evaluate antimutagenic potential of phytochemicals as Ames test.
Cite this as
2015. Screening of cytoprotectors against methotrexate-induced cytogenotoxicity from bioactive phytochemicals, by umu test combined with micronucleus Assay. PeerJ PrePrints 3:e1286v1 https://doi.org/10.7287/peerj.preprints.1286v1note This preprint is not peer-reviewed. You may wish to reference the subsequent peer-reviewed version of this article.
Author comment
Methotrexate (MTX) is one of the most intensively investigated and effective chemotherapeutic agents. However, a present study has confirmed that MTX induced cytotoxic and genotoxic effects in the germ cells. Furthermore, MTX chemotherapy for gestational trophoblastic tumors and acute lymphoblastic leukemia really increases the risk of second tumors. In this work, we explored an effective and quick method for screening potential antimutagens in bioactive phytochemicals based on umu assay coupled with micronucleus test. The results indicated that bioactive phytochemical combinations (grape seed proanthocyanidins and eleutherosides from siberian ginseng as well as green tea polyphenols and siberian ginseng extract) could be used as new cytoprotectors, besides umu test was the same effective assay to evaluate antimutagenic potential of phytochemicals as Ames test.
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Competing Interests
The authors declare that they have no competing interests.
Author Contributions
Shaobin Gu conceived and designed the experiments, performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Ying Wu performed the experiments, contributed reagents/materials/analysis tools, reviewed drafts of the paper.
Jianbo Yang conceived and designed the experiments.
Animal Ethics
The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):
Kunming specific pathogen-free mice were provided by the Henan Laboratory Animal Center. License number: SCXK (Yu) 2005-0001.The present study was conducted in accordance with the principles outlined in the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
Funding
This work was supported by Foundation for University Key Teacher by Henan Province (Grant No. 2014GGJS-056) and National Natural Science Foundation of China (Grant No. U1304307). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
