5 replies to this topic

[FunkOdyssey]

Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and
catechins.
Galati G, Lin A, Sultan AM, O'brien PJ
Free Radic Biol Med. 2006 Feb 15; 40(4): 570-80

Tea phenolic acids and catechins containing gallic acid moieties are most
abundant in green tea, and various medical benefits have been proposed from
their consumption. In the following, the cytotoxicities of these major tea
phenolics toward isolated rat hepatocytes have been ranked and the
mechanisms of cytotoxicity evaluated. The order of cytotoxic effectiveness
found was epigallocatechin-3-gallate > propyl gallate >
epicatechin-3-gallate > gallic acid, epigallocatechin > epicatechin. Using
gallic acid as a model tea phenolic and comparing it with the tea catechins
and gallic acid-derivative food supplements, the major cytotoxic mechanism
found with hepatocytes was mitochondrial membrane potential collapse and ROS
formation. Epigallocatechin-3-gallate was also the most effective at
collapsing the mitochondrial membrane potential and inducing ROS formation.
Liver injury was also observed in vivo when these tea phenolics were
administered ip to mice, as plasma alanine aminotransferase levels were
significantly increased. In contrast, GSH conjugation, methylation,
metabolism by NAD(P)H:quinone oxidoreductase 1, and formation of an iron
complex were important in detoxifying the gallic acid. In addition, for the
first time, the GSH conjugates of gallic acid and epigallocatechin-3-gallate
have been identified using mass spectrometry. These results add insight into
the cytotoxic and cytoprotective mechanisms of the simple tea phenolic acids
and the more complex tea catechins.

Edited by funkodyssey, 09 February 2006 - 09:24 PM.

[FunkOdyssey]

In this study, EGCG was the only catechin that was hepatotoxic, and it was only in a dose of 50mg/kg which seems crazy high:

http://toxsci.oxford...t/full/69/2/354

[ajnast4r]

thats liek 4500mg EGCG in a 200lb adult.... i dont think anyone here consumes much over 1000.

i dont think this is a worry at all, especially considered the NUMEROUS benefits of a good green tea extract.

[FunkOdyssey]

I know green tea and its extract have many well-documented benefits, but I thought this was still worthy of some discussion. I mean... "Epigallocatechin-3-gallate was also the most effective at collapsing the mitochondrial membrane potential and inducing ROS formation." That's not something you want to hear about a substance many of us are deliberately ingesting for health purposes.

[ajnast4r]

at doses of 4.5 GRAMS... no one ever takes that much.

the most ive ever heard of anyone taking is 1 gram per day... i personally take between 250mg-1g(total catechins) depending on how i feel, and how much tea i actually drink.

also, is this isolated EGCG?(do they even make a synth of this)

[trh001]

See snipet from discussion: it was IP administered, NOT oral . I'd watch the literature, but note the authors discussion of their own results, below...

"The ip administration route may therefore normally have no toxic implications. "

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Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and
catechins.
Galati G, Lin A, Sultan AM, O'brien PJ
Free Radic Biol Med. 2006 Feb 15; 40(4): 570-80

Due to its central role in drug metabolism, the liver is particularly susceptible to injury following systemic exposure to xenobiotics by ip administration. To test whether hepatocytes are susceptible to tea catechins or gallic acid in vivo as shown here for hepatocytes in vitro, the hepatotoxicity of these dietary phenolics in vivo was therefore tested in mice by ip administration. It was found that the dietary phenolics NDGA, gallic acid, propyl gallate, tannic acid, and EGCG, administered ip, all significantly increased plasma ALT levels, at various doses, compared to the control. The order of hepatotoxic effectiveness found, using a plasma ALT level of approximately 200 U/L (a 4-fold increase compared to control), was as follows: NDGA (50 mg/kg) > tannic acid, EGCG (both approximately 120 mg/kg) > propyl gallate (170 mg/kg) >> gallic acid (500 mg/kg). Surprisingly, the most abundant tea catechin (EGCG) caused death to mice in less than 24 h at a dose of 150 mg/kg. NDGA has previously been shown to have an LD50 (ip), after 5 days, of 75 mg/kg and to cause 100% mortality by ip injection at 100 and 500 mg/kg after 30 h in female Balb/c mice [43]. Interestingly, we found that a lower concentration of EGCG (150 mg/kg) caused 100% mortality in male CD-1 mice in 24 h. NDGA, a polyphenolic component of chaparral tea, has also been implicated in published case studies of hepatotoxicity that developed in users of chaparral tea [17].

However, normal exposure to tea flavonoids or gallic acid occurs by the oral route and the liver is mostly exposed to flavonoid phase II conjugates formed when the flavonoid or gallic acid is transported across the intestinal cell. The ip administration route may therefore normally have no toxic implications. Recently, the no-observed-adverse-effect level for feeding a gallic acid-containing diet for 13 weeks to male F344 rats was found to be 119 mg/kg/day. Centrilobular liver cell hypertrophy was observed at 1.7% gallic acid, whereas hemolytic anemia of weak severity developed at 5% gallic acid [44].

In conclusion, we have presented significant evidence in support of a cytotoxic mechanism for tea catechins and simple phenolics involving mitochondrial toxicity and ROS formation (prooxidant activity). Interestingly, the most abundant tea phenolic, EGCG, was also by far the most cytotoxic to isolated rat hepatocytes and hepatotoxic to mice in vivo. We have also obtained evidence indicating that these dietary gallic acid derivatives were detoxified by NQO1, GSH, and COMT to nontoxic species.