Dietary Quercetin, Immune Functions and Colonic Carcinogenesis in Rats

Exon, Jerry H.; Magnuson, Bernadene A.; South, Elizabeth H.; Hendrix, Kyle

doi:10.3109/08923979809034816

Cited by 33 publications

(19 citation statements)

References 33 publications

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“…A metaanalysis of 4 polyp-recurrence human intervention trials and 4 carcinogen-treated animal studies indicated that there was no protective effect of β-carotene supplementation [4] against colon tumor formation. Quercetin supplementation studies also showed inconsistent results in carcinogen-treated colon cancer models [1,5,13,17]. These results and the results from the present study suggest that it may be too early to conclude dietary quercetin and β-carotene are effective in colon cancer prevention, and more in vivo intervention studies are required.…”

Section: Discussioncontrasting

confidence: 59%

Effects of quercetin and β‐carotene supplementation on azoxymethane‐induced colon carcinogenesis and inflammatory responses in rats fed with high‐fat diet rich in ω‐6 fatty acids

et al. 2006

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Chronic inflammation in gastrointestinal tract has been suggested as a risk factor for tumor formation. The effect of dietary supplementation of quercetin or beta-carotene on colon carcinogenesis and inflammatory response in rats fed with high-fat diet rich in omega-6 fatty acids was assessed. Animals were exposed to two weekly subcutaneous injections of AOM (azoxymethane) at a single dose of 15 mg/kg body weight. A portion of rats from each group was sacrificed at 8 weeks after the last AOM treatment to determine ACF (aberrant crypt foci) formation. Colonic mucosa expression of iNOS (inducible nitric oxide) and COX-2 (cyclooxygenase-2) protein, and blood PGE2 (prostaglandin E2) level were measured. The remaining groups of animals were sacrificed at 33 weeks after the last AOM treatment to examine colon tumor formation. Rats on high-fat diet developed more aberrant crypt foci (P<0.05) compared with those of rats on regular diet. In the same vein, but in contrast to the effect seen with regular diet, the high-fat diet induced a significant up-regulation of iNOS expression. There was no significant change in the extent of COX-2 expression or in the PGE2 levels. Quercetin or beta-carotene supplementation reduced the number of ACF only in animals fed high-fat diet (p<0.05), however, no significant difference in tumor incidence was found. At week 33, the expression of iNOS was reduced by quercetin without a statistical significance, and COX-2 expression was slightly reduced in rats on beta-carotene supplementation. No change in PGE2 levels was observed. Whilst dietary antioxidants are considered as effective suppressors for precancerous lesion formation in colons exposed to high-risk diet, it is clear that elucidating the role of individual antioxidants in colon tumor formation coupled with an understanding of the molecular mechanisms involved would benefit colon cancer prevention strategies.

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Section: Discussioncontrasting

confidence: 59%

Effects of quercetin and β‐carotene supplementation on azoxymethane‐induced colon carcinogenesis and inflammatory responses in rats fed with high‐fat diet rich in ω‐6 fatty acids

et al. 2006

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“…Several studies have investigated the effect of wine flavonoids on NK cell function. While quercetin in vitro (1 mM) significantly decreased lytic activity of NK cells (no effects at lower concentrations) (Exon et al, 1998), in animal models, quercetin (100 mg/kg) and catechin (125-500 mg/kg) increased lytic activity of NK cells (Ikeda et al, 1984;Exon et al, 1998). The doses used in in vitro studies and those obtained in the animal studies were much higher than the plasma flavonoid concentrations in our study subjects after a single intake of these beverages.…”

Section: Discussionmentioning

confidence: 49%

Daily moderate amounts of red wine or alcohol have no effect on the immune system of healthy men

et al. 2003

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Objective: To investigate whether the daily intake of red wine (RW) at a dose which inversely correlates with cardiovascular disease (CVD) risk modulates immune functions in healthy men. Design: Randomized single-blind trial with four intervention periods. Setting: The Institute of Nutritional Physiology, Federal Research Centre for Nutrition, Karlsruhe, Germany. Subjects: A total of 24 healthy males with moderate alcohol consumption patterns were recruited and all completed the study. Intervention: Participants consumed 500 ml of RW (12% ethanol (ETOH)) or 500 ml of a 12% ETOH dilution per day for a period of 2 weeks. To control the potential effects of RW polyphenols, accordingly 500 ml/day of dealcoholized red wine (DRW) and of red grape juice (RGJ) were given. The following immune parameters were measured before beverage consumption and at 1 and 2 weeks following beverage consumption: phagocytic activity of neutrophils and monocytes, production of tumor necrosis factor-alpha (TNFa), interleukin-2 and -4, transforming growth factor-b, TNFa mRNA, lymphocyte proliferation, lytic activity of natural killer cells, and percentage of apoptotic lymphocytes. Results: Consumption of a moderate volume of alcohol with RW and with a 12% ETOH dilution had no effect on immune functions in healthy males. Consumption of polyphenol-rich beverages (DRW and RGJ) did not affect immunity-related parameters. Conclusions: Daily moderate consumption of alcohol and of RW for 2 weeks at doses which inversely correlate with CVD risk has no adverse effects on human immune cell functions. Polyphenol-rich beverages such as RGJ and DRW further do not suppress immune responses in healthy men.

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“…No specific biological pathways were modulated in the ileum and only a single, yet highly relevant, pathway was identified in the colon (antigen presentation). Interestingly, the great majority of studies examining quercetin in the intestine have focused on its role on cell proliferation, apoptosis, and carcinogenesis, while little work has focused on its role in immune function (11). This fact may stem from the use of common carcinomic cell culture models (e.g., Caco-2, HT-29, T84 cells, etc.)…”

Section: Discussionmentioning

confidence: 99%

Hepatic cytochrome P-450 reductase-null mice show reduced transcriptional response to quercetin and reveal physiological homeostasis between jejunum and liver

Mutch¹,

Crespy²,

Clough³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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P-450reductase-null mice show reduced transcriptional response to quercetin and reveal physiological homeostasis between jejunum and liver. Am J Physiol Gastrointest Liver Physiol 290: G63-G72, 2006. First published February 2, 2006 doi:10.1152/ajpgi.00565.2005.-Using mice deficient in hepatic cytochrome P-450 oxidoreductase (POR), which disables the liver cytochrome P-450 system, we examined the metabolism and biological response of the anticarcinogenic flavonoid, quercetin. 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 two-to threefold more genes responded significantly to quercetin in WT compared with 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 was 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 1 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.

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Dietary Quercetin, Immune Functions and Colonic Carcinogenesis in Rats

Cited by 33 publications

References 33 publications

Effects of quercetin and β‐carotene supplementation on azoxymethane‐induced colon carcinogenesis and inflammatory responses in rats fed with high‐fat diet rich in ω‐6 fatty acids

Effects of quercetin and β‐carotene supplementation on azoxymethane‐induced colon carcinogenesis and inflammatory responses in rats fed with high‐fat diet rich in ω‐6 fatty acids

Daily moderate amounts of red wine or alcohol have no effect on the immune system of healthy men

Hepatic cytochrome P-450 reductase-null mice show reduced transcriptional response to quercetin and reveal physiological homeostasis between jejunum and liver

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