title: Effects of Epigallocatechin Gallate on Tert-Butyl Hydroperoxide-Induced Mitochondrial Dysfunction in Rat Liver Mitochondria and Hepatocytes.
abstract: Epigallocatechin gallate (EGCG) is a green tea antioxidant with adverse effects on rat liver mitochondria and hepatocytes at high doses. Here, we assessed whether low doses of EGCG would protect these systems from damage induced by tert-butyl hydroperoxide (tBHP). Rat liver mitochondria or permeabilized rat hepatocytes were pretreated with EGCG and then exposed to tBHP. Oxygen consumption, mitochondrial membrane potential (MMP), and mitochondrial retention capacity for calcium were measured. First, 50μM EGCG or 0.25 mM tBHP alone increased State 4 Complex I-driven respiration, thus demonstrating uncoupling effects; tBHP also inhibited State 3 ADP-stimulated respiration. Then, the coexposure to 0.25 mM tBHP and 50μM EGCG induced a trend of further decline in the respiratory control ratio beyond that observed upon tBHP exposure alone. EGCG had no effect on MMP and no effect, in concentrations up to 50μM, on mitochondrial calcium retention capacity. tBHP led to a decline in both MMP and mitochondrial retention capacity for calcium; these effects were not changed by pretreatment with EGCG. In addition, EGCG dose-dependently enhanced hydrogen peroxide formation in a cell- and mitochondria-free medium.Conclusion. Moderate nontoxic doses of EGCG were not able to protect rat liver mitochondria and hepatocytes from tBHP-induced mitochondrial dysfunction.
authors.affiliation: Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic; Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Vojtech
authors.identifier: 0000-0002-8679-5208
authors.initials: V
authors.lastname: Mezera
authors.affiliation: Department of Anatomy, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
authors.forename: Rene
authors.initials: R
authors.lastname: Endlicher
authors.affiliation: Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
authors.forename: Otto
authors.identifier: 0000-0002-5251-5343
authors.initials: O
authors.lastname: Kucera
authors.affiliation: Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Sobotka
authors.affiliation: Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Drahota
authors.affiliation: Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
authors.forename: Zuzana
authors.identifier: 0000-0002-3908-290X
authors.initials: Z
authors.lastname: Cervinkova
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
chemical_list: D002392:Catechin; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D002118:Calcium