Potential role of the mitochondria as a target for the hepatotoxic effects of (-)-epigallocatechin-3-gallate in mice

Karma D. James, Mary J. Kennett, Joshua D. Lambert

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Green tea and (-)-epigallocatechin-3-gallate (EGCG) have been studied for their obesity-related health effects. Many green tea extract (GTE)-based dietary supplements are commercially-available. Although green tea beverage has a long history of safe use, a growing number of case-reports have linked GTE-based supplements to incidents of hepatotoxicity. Animal studies support the hepatotoxic potential of GTE and EGCG, but the mechanisms remain unclear. Here, we examined the hepatotoxic effects of EGCG in C57BL/6J mice and evaluated changes in hepatic antioxidant response and mitochondria structure and function. Intragastric dosing with EGCG (500 - 750 mg/kg) once daily for 3 d caused hepatic inflammation, necrosis, and hemorrhage. Hepatotoxicity was associated with increased oxidative stress and decreased superoxide dismutase and glutathione peroxidase levels. Real-time PCR and transmission electron microscopy showed decreased hepatic mitochondria copy number in EGCG-treated mice. The mRNA levels of marker genes of respiratory complex I and III, sirtuin 3, forkhead box O3a, and peroxisome-EGCG-treated mice. Sirtuin 3 protein levels were also decreased by EGCG. Our data indicate the mitochondria may be a target for EGCG, and that inhibition of mitochondria function/antioxidant response may be important for the hepatotoxicity of bolus EGCG.

Original languageEnglish (US)
Pages (from-to)302-309
Number of pages8
JournalFood and Chemical Toxicology
Volume111
DOIs
StatePublished - Jan 1 2018

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Mitochondria
epigallocatechin
mitochondria
green tea
Tea
mice
Sirtuin 3
hepatotoxicity
liver
Liver
extracts
Dietary supplements
Antioxidants
Electron Transport Complex I
antioxidants
epigallocatechin gallate
Peroxisomes
Oxidative stress
Beverages
peroxisomes

All Science Journal Classification (ASJC) codes

  • Food Science
  • Toxicology

Cite this

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title = "Potential role of the mitochondria as a target for the hepatotoxic effects of (-)-epigallocatechin-3-gallate in mice",
abstract = "Green tea and (-)-epigallocatechin-3-gallate (EGCG) have been studied for their obesity-related health effects. Many green tea extract (GTE)-based dietary supplements are commercially-available. Although green tea beverage has a long history of safe use, a growing number of case-reports have linked GTE-based supplements to incidents of hepatotoxicity. Animal studies support the hepatotoxic potential of GTE and EGCG, but the mechanisms remain unclear. Here, we examined the hepatotoxic effects of EGCG in C57BL/6J mice and evaluated changes in hepatic antioxidant response and mitochondria structure and function. Intragastric dosing with EGCG (500 - 750 mg/kg) once daily for 3 d caused hepatic inflammation, necrosis, and hemorrhage. Hepatotoxicity was associated with increased oxidative stress and decreased superoxide dismutase and glutathione peroxidase levels. Real-time PCR and transmission electron microscopy showed decreased hepatic mitochondria copy number in EGCG-treated mice. The mRNA levels of marker genes of respiratory complex I and III, sirtuin 3, forkhead box O3a, and peroxisome-EGCG-treated mice. Sirtuin 3 protein levels were also decreased by EGCG. Our data indicate the mitochondria may be a target for EGCG, and that inhibition of mitochondria function/antioxidant response may be important for the hepatotoxicity of bolus EGCG.",
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Potential role of the mitochondria as a target for the hepatotoxic effects of (-)-epigallocatechin-3-gallate in mice. / James, Karma D.; Kennett, Mary J.; Lambert, Joshua D.

In: Food and Chemical Toxicology, Vol. 111, 01.01.2018, p. 302-309.

Research output: Contribution to journalArticle

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