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, 50 μM 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 50 μM 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 50 μM, 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.

Epigallocatechin-3-Gallate (EGCG), An Active Constituent of Green Tea: Implications in the Prevention of Liver Injury Induced by Diethylnitrosamine (DEN) in Rats

“…Mitochondria are the major source of endogenous reactive oxygen species, and altering mitochondrial homeostasis is a known mechanism for toxic compounds, including DEN [40,41]. EGCG treatment significantly improves mitochondrial health and number as determined by our TEM study; several studies [42][43][44] with EGCG are in accordance with our study. Further studies are needed to fully investigate this mechanism.…”

The Role of Catechins in Cellular Responses to Oxidative Stress

“…Mitochondrial complex III, IV, and V components were up-regulated after culture with the monomer-rich fraction, corresponding with increased cellular ATP production [ 86 ]. Epigallocatechin gallate (the main catechin of green tea), at the concentration of 50 μM, increased State 4 complex I-driven respiration, thus demonstrating uncoupling effects on rat liver mitochondria [ 87 ]. Furthermore, epigallocatechin gallate increased oxidative phosphorylation and ATP production in both human cultured astrocytes and neurons with different kinetic parameters and without toxicity [ 88 ].…”

Reprogramming of leukemic cell metabolism through the naphthoquinonic compound Quambalarine B

“…Oroboros software Datlab 5 version 5.1.0.20 (Oroboros Instruments Corp, Innsbruck, Austria) was used for calculating oxygen uptake rates and for presenting the oxygraphic curve. Oxygen uptake in isolated mitochondria is expressed as pmol/s/mg protein [ 50 ]. Presented data are subject of three independent experiments performed in technical duplicates.…”