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Biotoxicological Analyses of Trimeroside from Baccharis trimera Using a Battery of In Vitro Test Systems.

ABSTRACT: The use in folk medicine of Baccharis trimera and recent studies on DNA damage by oxidative stress mechanisms have motivated this study. We investigated the biotoxicological effects of trimeroside from this plant. Aqueous extract from aerial parts of B. trimera was fractioned by flash chromatography for further isolation by thin-layer chromatography. The novel nor-monoterpene glycoside, trimeroside, and three flavonoids, cirsimaritin, luteolin and quercetin, were isolated. The genotoxic and mutagenic potential of trimeroside was determined by Salmonella/microsome (TA98 and TA100), comet assay, and cytokinesis-block micronucleus cytome assay (CBMN-cyt) in HepG2 cells. We also screened trimeroside into different human tumoral cell lines by sulforhodamine B (SRB) assay. Mutagenicity was detected in TA100 strain with metabolic activation. Genotoxic effects were not observed in HepG2 by comet assay. However, a decrease in the nuclear index division in the 2.0?mg·mL^-1 concentration and an increase of nucleoplasmic bridges in the 1.5?mg·mL^-1 concentration were detected by CBMN-cyt assay indicating cytotoxic and mutagenic effects. In SRB assay, trimeroside showed weak antiproliferative activity against the cell lines.

SUBMITTER: Dos Santos MS

PROVIDER: S-EPMC6120265 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Biotoxicological Analyses of Trimeroside from Baccharis trimera Using a Battery of In Vitro Test Systems.

Dos Santos Marcela Silva MS da Silva Juliana J Menezes Ana Paula Simões APS de Barros Francisco Maikon Corrêa FMC Lemes Maria Luisa Brodt MLB Rossatto Raíssa R RR Feistel Cleverson C de Almeida Indara Dedigo ID Grivicich Ivana I Prado Lismare L Picada Jaqueline Nascimento JN de Barros Falcão Ferraz Alexandre A

Oxidative medicine and cellular longevity 20180819

The use in folk medicine of Baccharis trimera and recent studies on DNA damage by oxidative stress mechanisms have motivated this study. We investigated the biotoxicological effects of trimeroside from this plant. Aqueous extract from aerial parts of B. trimera was fractioned by flash chromatography for further isolation by thin-layer chromatography. The novel nor-monoterpene glycoside, trimeroside, and three flavonoids, cirsimaritin, luteolin and quercetin, were isolated. The geno ...[more]

PMID: 30210656

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Project description:For assessing the cancer-causing potential for humans of a chemical compound, the conventional approach is the use of the 2-year rodent carcinogenicity bioassay, thus alternatives such as in vitro toxicogenomics are highly desired. In the present study, the transcriptomics responses following exposure to genotoxic (GTX) and non-genotoxic (NGTX) hepatocarcinogens and non-carcinogens (NC) in five liver-based in vitro models, namely conventional and epigenetically-stabilized cultures of primary rat hepatocytes, the human hepatoma-derived HepaRG and HepG2 cell lines and the human embryonic stem cell-derived hepatocyte-like cells hES-Heps are examined and compared. The global gene expression profiles of five commonly used liver-based in vitro systems are investigated, namely conventional cultures of primary rat hepatocytes (HepsC), Trichostatin A (TSA)-stabilized cultures of primary rat hepatocytes (HepsT), human embryonic stem cell-derived hepatocyte-like cells (hES-Hep), HepG2 and HepaRG cells. These models are exposed to 15 prototypical compounds which have been carefully chosen and belong to 3 toxic classes i.e. (i) genotoxic (GTX) (aflatoxin B1, AFB1; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NNK; 2-nitrofluorene, 2NF; benzo(a)pyrene, BaP; cyclophosphamide, CYCLO), (ii) non-genotoxic (NGTX) (methapyrilene hydrochloride, MPH; piperonylbutoxide , PIPB; Wy-14643, WYE; phenobarbital sodium, SPB; 12-O-tetradecanoylphorbol-13-acetate, TPA) carcinogens and (iii) non-carcinogens (NC) (nifedipine, NIF; clonidine, CND; D-mannitol, MAN; tolbutamide, TOL; diclofenac sodium, SDF). For the gene- and pathway- based analysis, the raw microarray data was re-annotated to Ensembl version 61 genome and Gene Chip Robust Multi-array Average (GC-RMA) normalized (Dai et al. 2005). This resulted in 11,187 and 18,919 probe sets for the rat and the human models, respectively. For the classification analysis, the raw microarray data was annotated using the chip description files from Affymetrix and then GC-RMA normalized. In order to eliminate batch effects, data from the different studies were half-z normalized. Half-z-normalization adjusts the logarithmic expression values of transcripts within a group such that each transcript has zero mean.

Dataset Information

Biotoxicological Analyses of Trimeroside from Baccharis trimera Using a Battery of In Vitro Test Systems.

Publications

Biotoxicological Analyses of Trimeroside from <i>Baccharis trimera</i> Using a Battery of <i>In Vitro</i> Test Systems.

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