Screening of cytoprotectors against methotrexate-induced cytogenotoxicity from bioactive phytochemicals, by umu test combined with micronucleus Assay

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.