Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA267014 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Given the positive results of quercetin in in vitro genotoxicity studies, it is of interest to test the in vivo genotoxicity of this important dietary flavonoid, especially considering possible high intake by widely available supplements. In the present study quercetin was tested in a transcriptomic analysis for genotoxicity in liver and small intestine of mice. Quercetin (0.33%) supplemented to a high-fat diet was administered to mice during 12 weeks and compared with high-fat diet feeding. Serum ALT and AST levels revealed no indications for hepatotoxicity. General microarray pathway analysis of liver and small intestinal tissue samples showed no regulation of genotoxicity related pathways. In addition, analysis of DNA damage pathways in these samples, also did not point at genotoxicity. Furthermore, comparison with a published classifier set of transcripts for identifying genotoxic compounds did not reveal any similarities with the regulation of these classifier set of transcripts by quercetin, except for two of the transcripts which were regulated in opposite direction. Available microarray datasets of known genotoxic compounds, 2-acetylaminofluorene (2-AAF) and aflatoxin B1 (AFB1) in mice were taken along as positive controls for comparison, and indeed showed genotoxic properties (regulation of genotoxic related genes) in the analyses. This transcriptomic study showed that supplementation with quercetin at ~350 mg/kg bw/day for 12 weeks in mice gave no indications of quercetin-induced genotoxicity in liver and small intestine.
2015-10-01 | GSE63227 | GEO
Project description:Both the 0.05% and 1% querceitn diets did not significantly affect the body weight, fat accumulation, and blood components. However, 0.05% quercetin significantly increased the glutathione/oxidized glutathione ratio in the liver. Moreover, the 1% quercetin diet reduced the lipid peroxidation markers 8-isoprostane in plasma and malondialdehyde in the liver, epididymal adipose tissues, and small intestine. Although comprehensive gene expression analysis dot not detect the genes with significantly different expression levels among the groups of mice, RT-PCR analysis showed that the 1% quercetin diet significantly induced the expression of the antioxidant enzymes Gpx1, Cat, and Sod1 in the liver and Gpx1 and Cat in the epididymal adipose tissues. The transcription factor nuclear factor E2-related factor 2 (Nrf2) was slightly induced in the nuclear fraction of the livers of mice fed the 1% quercetin diet. Quercetin may induce antioxidant enzymes by directly or indirectly activating the Nrf2 pathway in the liver. Five-week-old male mice were fed a AIN-93G diet containing 0% (Control), 0.05% (0.05% quercetin diet), or 1% quercertin (1% quercetin diet) for 20 weeks.
2015-07-24 | E-GEOD-62805 | biostudies-arrayexpress
Project description:Both the 0.05% and 1% querceitn diets did not significantly affect the body weight, fat accumulation, and blood components. However, 0.05% quercetin significantly increased the glutathione/oxidized glutathione ratio in the liver. Moreover, the 1% quercetin diet reduced the lipid peroxidation markers 8-isoprostane in plasma and malondialdehyde in the liver, epididymal adipose tissues, and small intestine. Although comprehensive gene expression analysis dot not detect the genes with significantly different expression levels among the groups of mice, RT-PCR analysis showed that the 1% quercetin diet significantly induced the expression of the antioxidant enzymes Gpx1, Cat, and Sod1 in the liver and Gpx1 and Cat in the epididymal adipose tissues. The transcription factor nuclear factor E2-related factor 2 (Nrf2) was slightly induced in the nuclear fraction of the livers of mice fed the 1% quercetin diet. Quercetin may induce antioxidant enzymes by directly or indirectly activating the Nrf2 pathway in the liver.
2015-07-24 | GSE62805 | GEO
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Keywords: nutritional intervention, comparative genomic response, genotype variation
2006-03-01 | GSE4259 | GEO
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Keywords: nutritional intervention, comparative genomic response, genotype variation
2006-03-01 | GSE4258 | GEO
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Keywords: nutritional intervention, comparative genomic response, genotype variation
2006-03-01 | GSE4257 | GEO
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Keywords: nutritional intervention, comparative genomic response, genotype variation
2006-03-01 | GSE4256 | GEO
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Experiment Overall Design: All animals were adapted to the RM3 (E) 801710 Soya-free powdered diet (B. S & S. [Scotland] Ltd, UK) over a period of 14 days. Quercetin was added separately to the semi-purified diets at a concentration of 6200 ppm (0.62 %; 6.2 g per kg). 65 male cytochrome P450 reductase null (KO) mice and 65 wild type (WT) C57BL/6 mice were reared, all aged between 6-8 weeks. Animals were housed 3 per cage, where both temperature and relative humidity were maintained within a range of 19-23oC and 40-70%, respectively. Twelve-hour periods of light were cycled with twelve-hour periods of darkness. Experiment Overall Design: For each strain of mouse, the following experimental design was used: a control group (25 mice) receiving powdered RM3 diet ad libitum and a group (25 mice) receiving a âhigh doseâ of quercetin (7 mg / mouse). The experimental diet was administered on day 15, following a 14-day adaptation period to the RM3 diet. Animals were sacrificed after 24 h. Experiment Overall Design: RNA samples destined for microarray analysis were only accepted and pooled into three groups if no aberrant signs of degradation (e.g. multiple peaks) were observed. The comprehensive gene expression profiles of the liver, jejunum, ileum, and colon were analyzed. In all cases, except those listed, RNA from 3 mice was pooled to form sample 1, another 3 mice to form sample 2, etc. Thus, 9 mice were used for the four experimental groups: wild-type, wild-type+quercetin, POR-null, POR-null+quercetin.
2008-06-13 | E-GEOD-4256 | biostudies-arrayexpress
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Experiment Overall Design: All animals were adapted to the RM3 (E) 801710 Soya-free powdered diet (B. S & S. [Scotland] Ltd, UK) over a period of 14 days. Quercetin was added separately to the semi-purified diets at a concentration of 6200 ppm (0.62 %; 6.2 g per kg). 65 male cytochrome P450 reductase null (KO) mice and 65 wild type (WT) C57BL/6 mice were reared, all aged between 6-8 weeks. Animals were housed 3 per cage, where both temperature and relative humidity were maintained within a range of 19-23oC and 40-70%, respectively. Twelve-hour periods of light were cycled with twelve-hour periods of darkness. Experiment Overall Design: For each strain of mouse, the following experimental design was used: a control group (25 mice) receiving powdered RM3 diet ad libitum and a group (25 mice) receiving a â??high doseâ?? of quercetin (7 mg / mouse). The experimental diet was administered on day 15, following a 14-day adaptation period to the RM3 diet. Animals were sacrificed after 24 h. Experiment Overall Design: RNA samples destined for microarray analysis were only accepted and pooled into three groups if no aberrant signs of degradation (e.g. multiple peaks) were observed. The comprehensive gene expression profiles of the liver, jejunum, ileum, and colon were analyzed. In all cases, except those listed, RNA from 3 mice was pooled to form sample 1, another 3 mice to form sample 2, etc. Thus, 9 mice were used for the four experimental groups: wild-type, wild-type+quercetin, POR-null, POR-null+quercetin.
2008-06-13 | E-GEOD-4259 | biostudies-arrayexpress
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Experiment Overall Design: All animals were adapted to the RM3 (E) 801710 Soya-free powdered diet (B. S & S. [Scotland] Ltd, UK) over a period of 14 days. Quercetin was added separately to the semi-purified diets at a concentration of 6200 ppm (0.62 %; 6.2 g per kg). 65 male cytochrome P450 reductase null (KO) mice and 65 wild type (WT) C57BL/6 mice were reared, all aged between 6-8 weeks. Animals were housed 3 per cage, where both temperature and relative humidity were maintained within a range of 19-23oC and 40-70%, respectively. Twelve-hour periods of light were cycled with twelve-hour periods of darkness. Experiment Overall Design: For each strain of mouse, the following experimental design was used: a control group (25 mice) receiving powdered RM3 diet ad libitum and a group (25 mice) receiving a âhigh doseâ of quercetin (7 mg / mouse). The experimental diet was administered on day 15, following a 14-day adaptation period to the RM3 diet. Animals were sacrificed after 24 h. Experiment Overall Design: RNA samples destined for microarray analysis were only accepted and pooled into three groups if no aberrant signs of degradation (e.g. multiple peaks) were observed. The comprehensive gene expression profiles of the liver, jejunum, ileum, and colon were analyzed. In all cases, except those listed, RNA from 3 mice was pooled to form sample 1, another 3 mice to form sample 2, etc. Thus, 9 mice were used for the four experimental groups: wild-type, wild-type+quercetin, POR-null, POR-null+quercetin.
2008-06-13 | E-GEOD-4257 | biostudies-arrayexpress