Peer Review #2 of "Screening of cytoprotectors against methotrexate-induced cytogenotoxicity from bioactive phytochemicals (v0.1)"

Abstract

As one of well known anti-neoplastic drugs, the cytogenotoxicity of methotrexate (MTX) has received more attention in recent years. To develop new cytoprotector to reduce the risk of second cancers caused by methotrexate, umu test combined with micronucleus assay was employed to estimated cytoprotective effects of ten kinds of bioactive phytochemicals and their combinations. The results showed that allicin, proanthocyanidins, polyphenols, eleutherosides and isoflavones owned higher antimutagenic activities than other phytochemicals. At the highest dose tested, the MTX genetoxicity was suppressed 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 exhibited stronger antimutagenic effects, the inhibition rate of methotrexate-induced genotoxicity separately reached 74.7 ± 6.5 % and 71.8 ± 4.7%. Pretreatment of Kunming mice with phytochemical combinations revealed a significant reduction in micronucleus and sperm abnormality rate following exposure to MTX (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.