Mitoquinone (mitoQ) Exerts Antioxidant Effects Independent of Mitochondrial Targeted Effects in Phorbol-12-myristate-13-acetate (PMA) or N-formyl-L-methiony-L-leucyl-L-phenylalanine (fMLP) Stimulated Polymorphonuclear Leukocyte (PMN) Superoxide (SO) Release

MitoQ is a mitochondrial-targeted coenzyme Q antioxidant analog that dose-dependently restored cardiac function and reduced infarct size in isolated perfused rat hearts subjected to ischemia reperfusion (I/R). Moreover, mitoQ also dose-dependently attenuated PMA stimulated PMN superoxide (SO) release at the same concentration (10uM) as the cardioprotective dose. NADPH oxidase is the principle source of PMN SO release. We speculate that mitoQ may exert antioxidant effects independent of the mitochondria. Therefore, we hypothesized that inhibition of mitoQ on PMN-SO release will be similar as other coenzyme Q analogs: coenzyme Q1 and decylubiquinone without affecting cell viability. SO release was measured spectrophotometrically from isolated rat PMNs measured by the reduction of ferricytochrome c and were stimulated with 100nM PMA. The absorbance was measured at 550 nm up to 360sec. Positive control samples were given SO dismutase (SOD; 10ug/ml) which inhibited PMA induced SO release by \u3e90%. MitoQ significantly inhibited SO release by 56 + 3% (10uM, n=10 ,

Combinational Effects of Apocynin and Mitoquinone in Reducing Myocardial Ischemia/reperfusion (MI/R) Injury

Reactive oxygen species (ROS) is generated due to the influx of oxygen during MI/R and contributes to post-reperfused cardiac contractile dysfunction and increased infarct size. Damaged mitochondria and NADPH oxidase activation are major sites of ROS in MI/R. In prior studies, apo, a NADPH oxidase inhibitor, and mitoQ, a mitochondrial-targeted antioxidant, dose-dependently improved post-reperfused left ventricular developed pressure (LVDP) and reduced infarct size in rat hearts subjected to I(30min)/R(45min). This led us to question whether low doses of apo and mitoQ given together can act synergistically to improve post-reperfused LVDP and reduce infarct size compared to either drug alone or control? Early data shows that the combination of apo (40μM) + mitoQ (1 μM ) (n=7) reduced infarct size to 27 ± 11% compared to mitoQ (1 μM) (n= 6) 54 ± 6% (