Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins

Galati, Giuseppe; Lin, Alison Li; Sultan, Amira M.; O’Brien, Peter J.

doi:10.1016/j.freeradbiomed.2005.09.014

Cited by 328 publications

(260 citation statements)

References 37 publications

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“…Although most of the potential health benefits of green tea and tea catechins have been attributed to their antioxidant properties, an increasing body of evidence suggests that polyphenols can behave as pro-oxidative agents. Experiments performed in rat liver cells showed that high concentrations of green tea extracts and of single tea phenolics are toxic; this cytotoxicity appears to be related to the gallic acid unit, and the most toxic compound was EGCG, while the least cytotoxic one was epicatechin (EC) [53,54]. Cytotoxicity was associated with reactive oxygen species formation and depletion of GSH; GSH-depleted hepatocytes were more susceptible to EGCG cytotoxicity and ROS formation, suggesting that GSH plays a role in detoxifying this compound [53].…”

Section: Discussionmentioning

confidence: 99%

“…(-)-Epigallocatechin gallate cytotoxicity and ROS formation increased significantly by dicumarol, a NAD(P) H:quinone oxidoreductase 1 (NQO1) inhibitor, thus suggesting that o-quinone metabolites of EGCG cause cytotoxicity and are reductively detoxified by NQO1 [53]. Treatment with the catechol-O-methyltranferase inhibitor, entacapone, was also found to cause a significant increase in EGCG cytotoxicity and ROS formation, thus suggesting that hepatocyte methylation plays a role in detoxifying this compound [53].…”

Section: Discussionmentioning

confidence: 99%

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Hepatotoxicity from green tea: a review of the literature and two unpublished cases

Mazzanti

Menniti‐Ippolito²,

Moro

et al. 2009

Eur J Clin Pharmacol

343

251

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Purpose To review the current literature on suspected green tea-related hepatic reactions and to describe two new cases reported within the framework of the Italian surveillance system of natural health products. Results A literature search of publication between 1999 and October 2008 retrieved 34 cases of hepatitis. Histological examination of the liver revealed inflammatory reactions, cholestasis, occasional steatosis, and necrosis. A positive dechallenge was reported in 29 cases. There was one reported death. A positive rechallenge occurred in seven cases (20%). In the two new cases, the causality assessment was judged as "possible" according to the RUCAM score. Conclusions Our analysis of the published case reports suggests a causal association between green tea and liver damage. The hepatotoxicity is probably due to (-)-epigallocatechin gallate or its metabolites which, under particular conditions related to the patient's metabolism, can induce oxidative stress in the liver. In a few cases, toxicity related to concomitant medications could also be involved.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity from green tea: a review of the literature and two unpublished cases

Mazzanti

Menniti‐Ippolito²,

Moro

et al. 2009

Eur J Clin Pharmacol

343

251

View full text Add to dashboard Cite

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“…Histological analysis revealed hemorrhagic lesions in the stomach and intestine. Intraperitoneal administration of EGCG to mice resulted in dose-dependent lethality beginning at 150 mg/kg (16). Lethality was associated with increases in serum ALT levels, suggesting the involvement of hepatotoxicity.…”

Section: Hepatic and Gastrointestinal Toxicities Of Green Tea Polyphementioning

confidence: 98%

“…Laboratory studies in rodents and dogs have supported the potential toxic effects of high doses of green tea-derived preparations (16,19). Oral administration (po) of Teavigo (a green tea polyphenol preparation containing 90% EGCG) or Polyphenon E for 13 or nine weeks, respectively, to Beagle dogs resulted in dose-dependent toxicity and death (19).…”

Section: Hepatic and Gastrointestinal Toxicities Of Green Tea Polyphementioning

confidence: 99%

Possible Controversy over Dietary Polyphenols: Benefits vs Risks

Lambert

Sang

Yang

2007

Chem. Res. Toxicol.

216

143

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“…These metabolites are hypothesized to arise from cysteine conjugation to the activated carbon in EGCG quinone. We and others have previously reported such reactions between EGCG and thiol-containing compounds such as cysteine and glutathione in cell culture and in vitro systems [14,15].…”

Section: Introductionmentioning

confidence: 75%

N-Acetylcysteine enhances the lung cancer inhibitory effect of epigallocatechin-3-gallate and forms a new adduct

Lambert

Sang

Yang

2008

Free Radical Biology and Medicine

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The major tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), inhibits carcinogenesis in many in vivo models. Many potential mechanisms of action have been proposed based on cell line studies, including pro-oxidant activity. In the present study, we studied the effect of N-acetylcysteine (NAC) on the inhibitory effects of EGCG on lung cancer cell growth. We found that NAC (0 -2 mM) dosedependently enhanced the growth inhibitory activity of EGCG against murine and human lung cancer cells. The combination of NAC and EGCG caused an 8.8-fold increase in apoptosis in CL13 mouse and H1299 human lung cancer cells compared to treatment with either agent alone. Addition of 2 mM NAC increased the stability of EGCG in the presence of CL13 cells (t 1/2 = 8.5 h vs. 22.7 h). Intracellular levels of EGCG were increased 5.5-fold by the addition of 2 mM NAC. HPLC and LC-MS analyses of cell culture medium from CL13 cells treated with EGCG and NAC for 24 h revealed that EGCG-2′-NAC was time-dependently formed. This adduct was not formed in the absence of NAC. The present results show that under cell culture conditions, EGCG and NAC interact to form a previously unreported adduct, EGCG-2′-NAC, which may contribute to enhancement of EGCGmediated cell killing.

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Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins

Cited by 328 publications

References 37 publications

Hepatotoxicity from green tea: a review of the literature and two unpublished cases

Hepatotoxicity from green tea: a review of the literature and two unpublished cases

Possible Controversy over Dietary Polyphenols: Benefits vs Risks

N-Acetylcysteine enhances the lung cancer inhibitory effect of epigallocatechin-3-gallate and forms a new adduct

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