Apocynin Exerts Dose-Dependent Cardioprotective Effects by Attenuating Reactive Oxygen Species in Ischemia/Reperfusion: A Recent Study | Chapter 2 | New Frontiers in Medicine and Medical Research Vol. 7

Because of increased reactive oxygen species and decreased endothelial-derived nitric oxide bioavailability, ischemia/reperfusion causes cardiac contractile failure and cell death. Endothelial dysfunction, which develops within 5 minutes of reperfusion, contributes to ischemia/reperfusion injury. Normally, NADPH oxidase creates reactive oxygen species to aid cell signalling and differentiation; however, excessive release of these species after ischemia exacerbates cell death. As a result, apocynin, a NADPH oxidase inhibitor, may help to preserve heart function and reduce infarct size after ischemia. Apocynin reduced leukocyte superoxide emission by 87 percent in a dose-dependent manner (40 (mu)M, 400 (mu)M, and 1 mM). After ischemia, isolated perfused hearts were given apocynin, which reduced infarct size to 39 7 percent (40 (mu)M), 28 4 percent (400 (mu)M; p 0.01), and 29 6 percent (1 mM; p 0.01), compared to 46 2 percent in the control group. This was linked to a reduction in final post-reperfusion left ventricular end-diastolic pressure, which fell from 60% in control hearts to 56.5% (40(mu)M), 43.4% (400(mu)M; p 0.01), and 48.5% (1 mM; p 0.05), respectively. Apocynin (13.7 mg/kg, I.V.) lowered H2O2 by approximately fourfold and enhanced endothelial function. During reperfusion, bioavailability increased nearly fourfold compared to controls (p 0.01), which was verified in in vivo rat hind limb ischemia/reperfusion models. These findings imply that apocynin inhibits NADPH oxidase-mediated reactive oxygen species release, which reduces ischemia/reperfusion-induced heart contractile failure and infarct size.

Author (S) Details

Qian Chen
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

C. Woodworth Parker
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

Issachar Devine
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

Regina Ondrasik
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

Tsion Habtamu
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

Kyle D. Bartol
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

Brendan Casey
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

Harsh Patel
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

William Chau
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

Tarah Kuhn
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

Lindon Young
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA.

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