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      Protective Effects of Silymarin and Silibinin against DNA Damage in Human Blood Cells


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          Silymarin (SM), a standardized extract derived from Silybum marianum (L.) Gaertn, is primarily composed of flavonolignans, with silibinin (SB) as its major active constituent. The present study aimed to evaluate the antigenotoxic activities of SM and SB using the alkaline comet assay in whole blood cells and to assess their effects on the expression of genes associated with carcinogenesis and chemopreventive processes. Different concentrations of SM or SB (1.0, 2.5, 5.0, and 7.5 mg/ml) were used in combination with the DNA damage-inducing agent methyl methanesulfonate (MMS, 800 μM) to evaluate their genoprotective potential. To investigate the role of SM and SB in modulating gene expression, we performed quantitative real-time PCR (qRT-PCR) analysis of five genes that are known to be involved in DNA damage, carcinogenesis, and/or chemopreventive mechanisms. Treatment with SM or SB was found to significantly reduce the genotoxicity of MMS, upregulate the expression of PTEN and BCL2, and downregulate the expression of BAX and ABL1. We observed no significant changes in ETV6 expression levels following treatment with SM or SB. In conclusion, both SM and SB exerted antigenotoxic activities and modulated the expression of genes related to cell protection against DNA damage.

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          Most cited references31

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            Alkylating agents, because of their ability to react directly with DNA either in vitro or in vivo, or following metabolic activation as in the case of the dialkylnitrosamines, have been used extensively in studying the mechanisms of mutagenicity and carcinogenicity. Their occurrence is widespread in the environment and human exposure from natural and pollutant sources is universal. Since most of these chemicals show varying degrees of both carcinogenicity and mutagenicity, and exhibit compound-specific binding patterns, they provide an excellent model for studying molecular dosimetry. Molecular dosimetry defines dose as the number of adducts bound per macromolecule and relates the binding of these adducts to the human mutagenic or carcinogenic response. This review complies DNA alkylation data for both methylating and ethylating agents in a variety of systems and discusses the role these alkylation products plays in molecular mutagenesis.
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              Absorption and metabolism of flavonoids.

              The benefits of flavonoids as chemopreventive dietary or dietary supplemental agents are still only "potential." Much has been learned about possible mechanisms of action of these agents, but whether they can reach their multiple intended sites of action, particularly in humans, is largely unknown. The biological fate of the flavonoids, including their dietary glycoside forms, is highly complex, dependent on a large number of processes. This review is intended to bring some order into this complex area and deals with the fate of the naturally occurring glycosides, their enzymatic hydrolysis, as well as the resulting aglycones. The impact of membrane transporters as well as metabolic enzymes on the cellular availability of these phytochemicals is examined. A reevaluation of the concept of oral bioavailability applied to the dietary flavonoids is presented.

                Author and article information

                Biomed Res Int
                Biomed Res Int
                BioMed Research International
                2 October 2018
                : 2018
                1Laboratório de Radiobiologia e Mutagênese, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Campus II, Goiânia, GO, Brazil
                2Laboratório de Mutagênese (LABMUT), Instituto de Ciências Biológicas, Universidade Federal de Goiás, Campus II, Goiânia, GO, Brazil
                3Laboratório de Biotecnologia, Câmpus Henrique Santillo, Universidade Estadual de Goiás, Anápolis, GO, Brazil
                4Núcleo de Pesquisas Replicon, Escola de Ciências Agrárias e Biológicas, Pontifícia Universidade Católica de Goiás, Goiânia, GO, Brazil
                Author notes

                Guest Editor: Claudio Tabolacci

                Copyright © 2018 Flávio Fernandes Veloso Borges et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
                Funded by: Universidade Estadual de Goiás
                Funded by: Fundação de Amparo à Pesquisa do Estado de Goiás
                Research Article


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