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

The Institute of Environmental and Human Health and Department of Environmental Toxicology, Texas Tech University, PO Box 41163, Lubbock, TX 79409-1163, USA.
Carcinogenesis (Impact Factor: 5.33). 02/2006; 27(2):262-8. DOI: 10.1093/carcin/bgi147
Source: PubMed


Modulation of urinary excretion of green tea polyphenols (GTPs) and oxidative DNA damage biomarker, 8-hydroxydeoxyguanosine (8-OHdG), were assessed in urine samples collected from a randomized, double-blinded and placebo-controlled phase IIa chemoprevention trial with GTP in 124 individuals. These individuals were sero-positive for both HBsAg and aflatoxin-albumin adducts, and took GTP capsules daily at doses of 500 mg, 1000 mg or a placebo for 3 months. Twenty-four hour urine samples were collected before the intervention and at the first and third month of the study. Urinary excretion of 8-OHdG and GTP components was measured by HPLC-CoulArray electrochemical detection. The baseline levels of 8-OHdG and GTP components among the three groups showed homogeneity (P > 0.70), and a non-significant fluctuation was observed in the placebo group over the 3 months (P > 0.30). In GTP-treated groups, epigallocatechin (EGC) and epicatechin (EC) levels displayed significant and dose-dependent increases in both the 500 mg group and 1000 mg group (P < 0.05). The 8-OHdG levels did not differ between the three groups at the 1 month collection, with medians of 1.83, 2.08 and 1.86 ng/mg-creatinine for placebo, 500 and 1000 mg group, respectively (P = 0.999). At the end of the 3 months' intervention, 8-OHdG levels decreased significantly in both GTP-treated groups, with medians of 2.02, 1.03 and 1.15 ng/mg-creatinine for placebo, 500 mg and 1000 mg group, respectively (P = 0.007). These results suggest that urinary excretions of EGC and EC can serve as practical biomarkers for green tea consumption in human populations. The results also suggest that chemoprevention with GTP is effective in diminishing oxidative DNA damage.

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    • "The two found in the highest amounts in green tea are EGC and EGCG. Both of these are excreted in bile, but EGC is also excreted in the urine, suggesting the possibility for green tea having antimicrobial activity in UTIs (Yang et al., 1998; Lee et al., 2002; Cabrera et al., 2006; Luo et al., 2006). Most of the studies on how these compounds accomplish the antibacterial activity have focused on EGCG. "
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    ABSTRACT: Background: Urinary tract infections (UTIs) are a very most common type of infection worldwide, and result in billions of dollars in medical care costs. Escherichia coli is the infective agent for 80–90% of all UTIs. Green tea, derived from leaves of the Camellia sinensis plant has been shown to have various potential health benefits (e.g., cardiovascular disease and cancer). The major beneficial components of green tea have been characterized, and are now known to be polyphenolic catechins. The main catechins in green tea are (-)-epicatechin-3-gallate, (-)-epigallocatechin (EGC), (-)-epicatechin, and (-)-epigallocatechin-3-gallate (EGCG). EGCG and EGC have been shown to have the greatest antimicrobial effects, but only EGC has been shown to be excreted in urine. Isolates of E. coli from UTIs collected between 2007 and 2008 were characterized for antimicrobial resistance to standard drugs. Then 80 of these isolates, representing a wide spectrum of antimicrobial susceptibility patterns, were selected for testing using an extract of green tea. Results: The concentrations of green tea extract tested were 0, 2.5, 3.0, 3.5, and 4.0 mg/ml. All of the strains tested, except one, had minimum inhibitory concentrations (MICs) of ≤4.0 mg/ml (99%), with 94% of the isolates having an MIC of ≤3.5 mg/ml, 76% of the isolates having an MIC of ≤3.0 mg/ml, 40% of the isolates having an MIC of ≤2.5 mg/ml. Two control strains varied in susceptibility, one having an MIC of ≤2.5 mg/ml,and the other having an MIC of ≤3.5 mg/ml. Conclusion: Since EGC has been shown to have antimicrobial effects on E. coli, and EGC has been shown to be excreted in the urine in a high enough concentration to potentially be effective as an antimicrobial; these MIC results suggest that ingesting green tea could have potential antimicrobial effects on UTIs caused by E. coli.
    Frontiers in Microbiology 06/2013; 4:162. DOI:10.3389/fmicb.2013.00162 · 3.99 Impact Factor
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    • "It was shown that AFB1-induced 8-OHdG was prevented by prior treatment with polyethylene glycol-conjugated catalase (PEG-CAT) in isolated mouse lung cells following in vivo treatment with the toxin (Guindon et al., 2007), but PEG-CAT was not protective against AFB1 carcinogenicity in mouse lung despite preventing DNA oxidation (Guindon et al., 2008). Luo et al. (2006) have shown that chemoprevention with green tea poliphenols is effective in diminishing oxidative DNA damage, through the reduction of the urinary 8-OHdG levels. "
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    ABSTRACT: Aflatoxins are naturally occurring mycotoxins that are produced by many species of Aspergillus, a fungus, mainly by Aspergillus flavus and Aspergillus parasiticus. Aflatoxins, especially aflatoxin B1 (AFB1), are very potent carcinogens in many species, including humans, birds, swine, fish, and rodents. The oxidative stress caused by AFB1 may be one of the underlining mechanisms for AFB1-induced cell injury and DNA, protein and lipid damages, which lead to tumorigenesis. This review presents an overview on aflatoxins and oxidative stress, with an emphasis on the protective role of the antioxidants.
    Toxin Reviews 11/2012; 31(3-4). DOI:10.3109/15569543.2012.730092 · 0.65 Impact Factor
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    • "At the end of the 3- months intervention, the levels of 8-hydroxydeoxyguanosine, an oxidative DNA damage biomarker, were statistically significant 50% lower in both green tea treated groups than in the placebo group (P = 0.007). There was no difference in urinary levels of aflatoxin B 1 mecapturic acids and 8-hydroxydeoxyguanosine between the 500-mg and 1000-mg green tea polyphenol groups [61]. These results suggest that the oral administration of green tea polyphenols at 500-1000 mg/day is effective in enhancing the detoxification of aflatoxin and reducing oxidative DNA damage. "
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    ABSTRACT: Experimental studies have consistently shown the inhibitory activities of tea extracts on tumorigenesis in multiple model systems. Epidemiological studies, however, have produced inconclusive results in humans. A comprehensive review was conducted to assess the current knowledge on tea consumption and risk of cancers in humans. In general, consumption of black tea was not associated with lower risk of cancer. High intake of green tea was consistently associated with reduced risk of upper gastrointestinal tract cancers after sufficient control for confounders. Limited data support a protective effect of green tea on lung and hepatocellular carcinogenesis. Although observational studies do not support a beneficial role of tea intake on prostate cancer risk, phase II clinical trials have demonstrated an inhibitory effect of green tea extract against the progression of prostate pre-malignant lesions. Green tea may exert beneficial effects against mammary carcinogenesis in premenopausal women and recurrence of breast cancer. There is no sufficient evidence that supports a protective role of tea intake on the development of cancers of the colorectum, pancreas, urinary tract, glioma, lymphoma, and leukemia. Future prospective observational studies with biomarkers of exposure and phase III clinical trials are required to provide definitive evidence for the hypothesized beneficial effect of tea consumption on cancer formation in humans.
    Pharmacological Research 03/2011; 64(2):123-35. DOI:10.1016/j.phrs.2011.03.002 · 4.41 Impact Factor
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