Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver cancer: modulation of urinary excretion of green tea polyphenols and 8-hydroxydeoxyguanosine (original) (raw)
Related papers
Validation of green tea polyphenol biomarkers in a phase II human intervention trial
Food and Chemical Toxicology, 2008
Health benefits of green tea polyphenols (GTPs) have been reported in many animal models, but human studies are inconclusive. This is partly due to a lack of biomarkers representing green tea consumption. In this study, GTP components and metabolites were analyzed in plasma and urine samples collected from a phase II intervention trial carried out in 124 healthy adults who received 500-or 1,000-mg GTPs or placebo for 3 months. A significant dose-dependent elevation was found for (-)-epicatechin-3-gallate (ECG) (p<0.001, trend test) and (-)-epigallocatechin-3-gallate (EGCG) (p<0.05, trend test) concentrations in plasma at both 1-month and 3-months after intervention with GTP. No significant increase of (-)-epicatechin (EC) or (-)-epigallocatechin (EGC) was observed in plasma after GTP intervention. A mixed-effects model indicated significant effects of dose (EGCG) and dose by time interaction (ECG), but not for EC and EGC. Analysis of phase 2 metabolic conjugates revealed a predominance of free GTPs in plasma, up to 85% for EGCG, while a majority of GTPs in urine were sulfated and glucuronidated conjugates (up to 100% for EC and 89% for EGC). These results suggest that plasma ECG and EGCG concentrations are reliable biomarkers for green tea consumption at the population level.
Carcinogenesis, 2000
nitrosodiethylamine-induced forestomach and lung tumors in 7322, USA mice and that both GTE and black tea extract (BTE) inhibited Email:vsly@nih.gov 4-(methylnitrosoamino)-1-butanone-induced lung adenomas, Black tea extracts (hot aqueous, polyphenols and theaflavalso in mice. Recently Rodgers et al. (21) showed black tea ins) and green tea extracts (hot aqueous, polyphenols, consumption could decrease mammary cancer in rats on high epicatechin, epicatechin gallate, epigallocatechin and epifat diets. gallocatechin gallate) were tested in nine standardized cell There has been extensive research into the possible mechanculture assays for comparative cancer chemopreventive isms of cancer prevention by tea extracts. Such mechanistic properties. Most black and green tea extracts strongly studies, especially with green tea polyphenols (GTPs) and inhibited neoplastic transformation in mouse mammary epigallocatechin gallate (EGCG), include inhibition of free organ cultures, rat tracheal epithelial cells and human lung radical formation and lipid peroxidation (22-31), the inhibition tumor epithelial cells. Nearly all tea fractions strongly of ornithine decarboxylase (ODC) (32-34), and the inhibition inhibited benzo[a]pyrene adduct formation with human of DNA-carcinogen binding and adduct formation (32,35).
Phytomedicine, 2011
Epidemiological data suggest that green tea (GT) consumption may protect against cardiovascular diseases (CVDs) and different types of cancer. This effect is attributed primarily to the antioxidant properties of flavanols from GT. This review provides an overview of controlled intervention studies investigating the effect of GT consumption on antioxidant effects ex vivo and in vivo. Methods: The Medline and Cochrane databases were searched independently by two investigators for controlled intervention studies (English) on GT consumption and antioxidant effects published up to June 2010. Thirty-one studies investigating antioxidant effects ex vivo [plasma antioxidant capacity (AC), DNA's resistance against oxidative induced damage) or in vivo (lipid and protein oxidation, DNA damage] met the criteria. Results were compared by considering the participants, the dose of GT, the amount of ingested flavanols, the duration of supplementation and the investigated biomarkers. Results: The comparison between the studies was difficult as relevant data, e.g., on flavanol concentration in plasma (10 of 31 studies) or on major antioxidants contributing to AC, were often missing. Lipid peroxidation and DNA damage were commonly investigated. Data on protein oxidation are scarce. An antioxidant effect of at least one parameter (increase in AC or reduction of oxidative stress marker) was observed in 15 out of 22 studies by daily consumption of GT, primarily in participants exposed to oxidative stress (smokers or mixed collectives of smokers and non-smokers and physical activity) and in 6 out of 9 studies investigating the bolus consumption of GT. Conclusion: There is limited evidence that regular consumption of GT in amounts of at least 0.6-1.5 l/day may increase AC and reduce lipid peroxidation (especially oxidation of LDL). This may contribute to the protection against CVDs and different types of cancer. Beneficial effects seem to be more likely in participants exposed to oxidative challenge.
Green tea or its concentrated extract is coveted for its health promoting catechin-like polyphenols, especially epigallocatechin-3-gallate (EGCG). However, its amicable efficacy is now being doubted considering the recent occurrence of several cases of hepato-and nephrotoxicity, after the ingestion of EGCG-fortified (≥85-90%) nutritional supplements. Therefore, the current study was carried out to ascertain the effect of green tea leaves extract (GTE), having low EGCG content (73.8%), on liver and kidney functions of male Wistar rats using various in vivo experiments and in vitro radical scavenging activity. In terms of acute toxicity, GTE was observed to be safe when delivered at a dosage of 2000 mg kg À1 body weight (BW). Oral delivery of GTE for 28 days at a concentration of 200 mg kg À1 BW/day did not trigger sub-acute toxicity to the liver and kidneys, as per serum biochemical analyses and histopathological examination. In contrast, GTE counteracted the effects of carbon tetrachloride (a potent hepato-degenerative compound) on the liver. Furthermore, increase in high-density lipoproteindcholesterol with concomitant lowering of serum triglycerides and low-density lipoproteindcholesterol were noticed in GTE-treated rats. These findings suggest that low EGCG p
Journal of Nutritional Biochemistry, 2005
Tea polyphenols have strong in vitro antioxidant activity. Due to their limited bioavailability, however, their contribution to in vivo antioxidant activity may depend on the form of administration. A human intervention study was performed to evaluate the bioavailability and antioxidant capacity of (À)-epigallocatechin-3-gallate (EGCG) administered as a single large dose in the form of either purified EGCG or as green tea extract (Polyphenon E). Plasma concentrations of tea polyphenols were determined by high-performance liquid chromatography (HPLC) analysis combined with coulometric array electrochemical detection (ECD). We found no differences in plasma EGCG concentrations and trolox equivalents determined by the trolox equivalent antioxidant capacity assay after administration of either form of EGCG. However, we found that the plasma antioxidant activity was significantly affected by changes in the plasma urate concentration, which may have interfered with the effect of tea polyphenols on the antioxidant activity. In addition, lymphocyte 8-hydroxydeoxyguanosine to deoxyguanosine (8-OHdG/10 6 dG) ratios were determined by HPLC with ECD. The 8-OHdG/10 6 dG ratios did not change significantly during the 24 h following both EGCG interventions but correlated significantly within individuals determined during the two interventions separated by 1 week. In summary, changes in plasma uric acid due to dietary intake were significantly correlated to the plasma antioxidant activity and exerted a stronger influence on the plasma antioxidant activity compared with the EGCG intervention. In future studies of dietary effects on the plasma antioxidant capacity, changes in plasma uric acid will need to be closely monitored. D
Prevention of oxidative DNA damage in inner organs and lymphocytes of rats by green tea extract
European Journal of Nutrition, 2010
Background Consumption of green tea (GT) is associated with decreased incidences of specific forms of cancer in humans and it was postulated that its antioxidant (AO) properties may account for these effects. The evidence for AO effects of GT is mainly based on the results from in vitro experiments and on animal studies in which protection against chemically induced damage was monitored. Aim of the study The goal of the study was the investigation of the prevention of strand breaks and DNA migration attributable to endogenous oxidation of bases by GT extract (GTE) in inner organs and lymphocytes of untreated rats. In addition, immunological parameters and biochemical markers were monitored. Methods DNA migration was measured in hepatocytes, colonocytes and lymphocytes after consumption of a low (1.3 mg/kg bw per day, 5 days) and a high dose (6.5 mg/kg bw per day, 5 days) of GTE in COMET assays (n = 5 animals per group). In addition, immunological parameters (TNF-a, IFN-c, IL-4 and IL-10), the total AO capacity and oxidized low-density lipoproteins were determined in plasma.
Hepatology International, 2011
Purpose The goal of this study was to investigate whether daily administration of green tea is able to protect the liver injury induced by cholesterol. Methods Male Wistar rats (n = 24) were distributed into four groups: group 1, negative control; group 2, cholesterol at 1% (w/w) in the diet treated for 5 weeks; group 3, cholesterol at 1% treated for 5 weeks and green tea at 1% (w/v) in drinking water in the last week only and group 4, cholesterol and green tea at 1% in drinking water for 5 weeks. Results The results pointed out that treatment with green tea in the last week (group 3) showed mild degenerative changes of liver tissue in cholesterol exposed group when compared to group 2. Green tea aqueous extract was not able to reduce cholesterol levels, that is, no significant statistical differences (p [ 0.05) were noticed when compared to positive control group. Nevertheless, green tea was able to decrease oxidative deoxyribonucleic acid (DNA) damage either to peripheral blood or to liver cells as depicted by significant statistical differences (p \ 0.05) in the mean tail moment between groups treated with green tea and cholesterol and cholesterol only. Furthermore, histomorphometric analysis of COX-2 expression revealed that in groups exposed to green tea they were significantly decreased (p \ 0.05), regardless of time exposure adopted. Conclusion Taken together, our results suggest that daily administration of green tea for at least 7 days displays some preventive properties as indicated by COX-2 downregulation and decreased oxidative DNA damage.
Green tea in chemoprevention of cancer
Toxicological Sciences, 1999
The concept of prevention of cancer using naturally occurring substances that could be included in the diet consumed by the human population is gaining increasing attention. Tea, next to water, is the most popularly consumed beverage in the world and it is grown in about 30 countries. Abundant data, amassed from several laboratories around the world in the last ten years, provided convincing evidence that polyphenolic antioxidants present in tea afford protection against cancer risk in many animal-tumor bioassay systems. The epidemiological studies, though inconclusive, have also suggested that the consumption of tea is associated with a lowered risk of cancer. Much of this work has been done on green tea; less is known about black tea. Green tea contains many polyphenolic antioxidants, and (-)-epigallocatechin-3-gallate (EGCG) is the key polyphenolic antioxidant believed to be responsible for most of the cancer chemopreventive properties of green tea. This review will discuss these effects and the molecular mechanisms associated with the biological response to green-tea polyphenols.
Molecular Nutrition & Food Research, 2013
Scope: Tea polyphenols are metabolized by the colonic microflora yielding phenolic metabolites, which may contribute to the health benefits of tea. We determined the serum and urine concentrations of phenolic acids, hippuric acid, and polyhydroxyphenyl-␥-valerolactones during green tea (GT) and black tea (BT) administration. The effects of (-)-epigallocatechin gallate (EGCG) and 3,4-dihydroxyphenylacetic acid (3,4-DHPAA) alone and in combination on bioavailability, intracellular metabolism, and antiproliferative activity were determined in HCT-116 colon cancer cells. Methods and results: The concentration of phenolic metabolites was quantified by HPLC with electrochemical detection and MS. Urine concentrations of 4-hydroxyphenylacetic acid (4-HPAA), 3-hydroxyphenylacetic acid (3-HPAA), and polyhydroxy-␥-valerolactones were increased significantly in men drinking GT compared to control. Urine concentration of 3-O-methylgallic acid (3OMGA) was significantly increased in men drinking BT compared to control. Serum 3,4-DHPAA was significantly increased after consumption of GT and BT and 4-HPAA after GT consumption. In vitro treatment of HCT-116 colon cancer cells with 3,4-DHPAA and EGCG exhibited an additive antiproliferative effect, while methylation of 3,4-DHPAA was significantly decreased. 3OMGA exhibited the strongest antiproliferative activity among the phenolic acids. Conclusion: The consumption of both, GT and BT, was associated with a significant increase in urinary and serum phenolic acids.