TY - JOUR
T1 - Potential role of the mitochondria as a target for the hepatotoxic effects of (-)-epigallocatechin-3-gallate in mice
AU - James, Karma D.
AU - Kennett, Mary J.
AU - Lambert, Joshua D.
N1 - Funding Information:
The authors thank Drs. Yeyi Gu, Sudathip Sae-tan, Zachary Bitzer, and Sarah Forester for technical assistance. The authors thank Ms. Roberta Horner and the Penn State Animal Diagnostic Laboratory for preparation of liver samples for histopathological analysis. The authors thank Ms. Missy Hazen for technical assistance in performing TEM and interpreting the results of that analysis. This study was supported in part by grant no. AT004678 from the National Center for Complementary and Integrative Health (to JDL), a Penn State College of Agricultural Sciences Graduate Student Research grant (to KDJ), the Azzara Family Bioactives Award (to JDL), and USDA Hatch Project no. 4565 .
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/1
Y1 - 2018/1
N2 - 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.
AB - 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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U2 - 10.1016/j.fct.2017.11.029
DO - 10.1016/j.fct.2017.11.029
M3 - Article
C2 - 29175576
AN - SCOPUS:85034864827
SN - 0278-6915
VL - 111
SP - 302
EP - 309
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
ER -
