In vitro toxicity of epigallocatechin gallate in rat liver mitochondria and hepatocytes.
Epigallocatechin-3-gallate (EGCG) is the main compound of green tea with well-described antioxidant, anti-inflammatory, and tumor-suppressing properties. However, EGCG at high doses was reported to cause liver injury. In this study, we evaluated the effect of EGCG on primary culture of rat hepatocytes and on rat liver mitochondria in permeabilized hepatocytes. The 24-hour incubation with EGCG in concentrations of 10 μmol/L and higher led to signs of cellular injury and to a decrease in hepatocyte functions. The effect of EGCG on the formation of reactive oxygen species (ROS) was biphasic. While low doses of EGCG decreased ROS production, the highest tested dose induced a significant increase in ROS formation. Furthermore, we observed a decline in mitochondrial membrane potential in cells exposed to EGCG when compared to control cells. In permeabilized hepatocytes, EGCG caused damage of the outer mitochondrial membrane and an uncoupling of oxidative phosphorylation. EGCG in concentrations lower than 10 μmol/L was recognized as safe for hepatocytes in vitro.
Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
Otto
O
Kucera
Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
Vojtech
V
Mezera
Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
Alena
A
Moravcova
Department of Anatomy, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
Rene
R
Endlicher
Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
Halka
H
Lotkova
Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
Zdenek
Z
Drahota
Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
Zuzana
Z
Cervinkova
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013662:Tea / Q000737:chemistry / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017382:Reactive Oxygen Species; D013662:Tea; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate; D053148:Caspase 3