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(+)-Catechin inhibits heart mitochondrial complex I and nitric oxide synthase: functional consequences on membrane potential and hydrogen peroxide production

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Abstract

In order to study the in vitro effect of flavan-3-ol (+)-catechin on the enzymatic activities of mitochondrial complex I and nitric oxide synthase (mtNOS), as well as the consequences on the membrane potential and H2O2 production rate, isolated mitochondria from rat heart were exposed to 3 nM to 100 μM (+)-catechin. NADH–Q1 reductase (complex I) and mtNOS activities were inhibited 25% and 50%, respectively, by the addition of 10 nM (+)-catechin to the reaction medium. Moreover, in the nM range, (+)-catechin decreased state 4 mitochondrial membrane potential by about 10 mV, but failed to change the membrane potential measured in the presence of ADP. (+)-Catechin (10 nM) inhibited not only complex I activity, but also the H2O2 production rate (35%) sustained by malate–glutamate, in accordance with the decrease observed in mitochondrial membrane potential. Considering (+)-catechin concentrations lower than 10 nM, linear and positive correlations were obtained between mitochondrial complex I activity and either NO (r2 = 0.973) or H2O2 production rates (r2 = 0.958), suggesting a functional association among these parameters. Altogether, the results indicate that (+)-catechin, at nM concentrations, inhibits mitochondrial complex I activity, leading to membrane potential decline and consequently to reduction in H2O2 and NO production rates. The decrease in mtNOS activity could also be a consequence of the direct action of (+)-catechin on the NOS structure, this effect being in accordance with the functional interaction between complex I and mtNOS, as previously reported.

Graphical abstract: (+)-Catechin inhibits heart mitochondrial complex I and nitric oxide synthase: functional consequences on membrane potential and hydrogen peroxide production

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Publication details

The article was received on 20 Sep 2018, accepted on 29 Mar 2019 and first published on 02 Apr 2019


Article type: Paper
DOI: 10.1039/C8FO01843J
Citation: Food Funct., 2019, Advance Article

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    (+)-Catechin inhibits heart mitochondrial complex I and nitric oxide synthase: functional consequences on membrane potential and hydrogen peroxide production

    D. E. Iglesias, S. S. Bombicino, A. Boveris and L. B. Valdez, Food Funct., 2019, Advance Article , DOI: 10.1039/C8FO01843J

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