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.
Highlights
Epigallocatechin gallate (EGCG) is an important polyphenolic compound of green tea [1, 2]
After exposure to various concentrations of EGCG and/or tert-butyl hydroperoxide (tBHP), similar effects were observed in isolated mitochondria and in permeabilized hepatocytes: the State 4 leak respiration in the presence of substrates for Complex I but without adenosine diphosphate (ADP) was increased by the addition of 0.25 mM tBHP in both isolated mitochondria (p < 0.01) and in permeabilized hepatocytes (p < 0.05)
Treatment with tBHP led to a decline in mitochondrial retention capacity for calcium, illustrated by an early increase in fluorescence following the addition of CaCl2
Summary
Epigallocatechin gallate (EGCG) is an important polyphenolic compound of green tea [1, 2]. EGCG displayed toxicity on mitochondria in permeabilized hepatocytes [8] and on mitochondria in a hepatoma cell line [14]. We decided to test whether low concentrations of EGCG would alter mitochondrial dysfunction caused by tert-butyl hydroperoxide (tBHP). Tea extract but not EGCG alone was able to ameliorate tBHP-induced cell death in primary rat hepatocytes [30]. The effects of EGCG and tBHP on liver mitochondrial function have not yet been tested and will be the focus of the present study in two experimental models: permeabilized rat hepatocytes and isolated rat liver mitochondria. As will be shown by measurements of respiration, mitochondrial membrane potential, and calcium retention capacity, low concentrations of EGCG did not affect mitochondrial parameters but did not alter tBHP-induced mitochondrial dysfunction either. High concentrations of EGCG were even found to enhance the toxicity of tBHP
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