Combinatorial Effects of Apocynin (apo) and Mitoquinone (mitoQ) in Treatment of Myocardia Ischemia/Reperfusion (MI/R) Injury

Date of Award

2014

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Lindon Young, PhD

Second Advisor

Ruth Borghaei, PhD

Third Advisor

Robert Barsotti, PhD

Fourth Advisor

Marcus G Bell, PhD

Abstract

Reactive oxygen species (ROS) are generated due to the influx of oxygen during myocardial ischemia/ reperfusion (MI/R) injury 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. Prior studies have reported that either apocynin, a NADPH oxidase inhibitor, or mitoQ, a mitochondrial-targeted antioxidant, dose-dependently improved post-reperfused left ventricular developed pressure (L VDP) and reduced infarct size in isolated (ex-vivo) rat hearts subjected to I(30min)/ R(45min). This led to question whether sub- effective doses of apocynin and mitoQ given together can act synergistically to improve post-reperfused L VDP and reduce infarct size compared to either drug alone or control. Data from this study show that the combination of apo ( 40µM) + mitoQ (1 µM) (n=8) significantly reduced infarct size to 29 ± 3% compared to control IIR hearts (pand mitoQ I µM (51± 10% and 53± 8% of baseline), respectively. Collectively, the data suggests that the combination of sub-effective doses of apocynin + mitoQ acted additively/ synergistically reduce infarct size and improve some post-reperfused cardiac function parameters respectively.

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