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

• Published in: Food & function 2019-05, Vol.1 (5), p.2528-2537
• Main Authors: Iglesias, Darío E, Bombicino, Silvina S, Boveris, Alberto, Valdez, Laura B
• Format: Article
• Language: English
• Subjects: Animals; Catechin - pharmacology; Electron Transport Complex I - antagonists & inhibitors; Electron Transport Complex I - chemistry; Electron Transport Complex I - metabolism; Enzyme Inhibitors - pharmacology; Female; Heart - drug effects; Hydrogen Peroxide - metabolism; Kinetics; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondria - metabolism; Myocardium - chemistry; Myocardium - metabolism; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - chemistry; Nitric Oxide Synthase - metabolism; Rats; Rats, Sprague-Dawley
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c8fo01843j

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 H 2 O 2 production rate, isolated mitochondria from rat heart were exposed to 3 nM to 100 μM (+)-catechin. NADH-Q 1 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 H 2 O 2 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 ( r 2 = 0.973) or H 2 O 2 production rates ( r 2 = 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 H 2 O 2 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. The aim was to study the in vitro effect of nM to low μM concentration of (+)-catechin on the enzymatic activities of mitochondrial complex I and mtNOS, as well as the consequences on the membrane potential and H 2 O 2 production rate.