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1 Section of Emergency Medicine and 2 Pulmonary Critical Care, Department of Medicine, 3 Emergency Resuscitation Center, 4 Department of Anesthesia and Critical Care and 5 Tang Center for Herbal Medicine Research, 6 Department of Radiation and Cellular Oncology, and 7 Center for Low Frequency EPR Imaging for In Vivo Physiology, University of Chicago, Chicago, Illinois 60637; and 8 Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, and Medical Biotechnology Center, University of Maryland, Baltimore, Maryland 21210
Flavonoids within Scutellaria baicalensis may be potent antioxidants on the basis of our studies of S. baicalensis extract. To further this work, we studied the antioxidative effects of baicalein, a flavonoid component of S. baicalensis, in a chick cardiomyocyte model of reactive oxygen species (ROS) generation during hypoxia, simulated ischemia-reperfusion, or mitochondrial complex III inhibition with antimycin A. Oxidant stress was measured by oxidation of the intracellular probes 2',7'-dichlorofluorescin diacetate and dihydroethidium. Viability was assessed by propidium iodide uptake. Baicalein attenuated oxidant stress during all conditions studied and acted within minutes of treatment. For example, baicalein given only at reperfusion dose dependently attenuated the ROS burst at 5 min after 1 h of simulated ischemia. It also decreased subsequent cell death at 3 h of reperfusion from 52.3 ± 2.5% in untreated cells to 29.4 ± 3.0% (with return of contractions; P < 0.001). In vitro studies using electron paramagnetic resonance spectroscopy with the spin trap 5-methoxycarbonyl-5-methyl-1-pyrroline-N-oxide revealed that baicalein scavenges superoxide but does not mimic the effects of superoxide dismutase. We conclude that baicalein can scavenge ROS generation in cardiomyocytes and that it protects against cell death in an ischemia-reperfusion model when given only at reperfusion.
Scutellaria baicalensis; ischemia; reactive oxygen species; 2',7'-dichlorofluorescin diacetate; antimycin A; dihydroethidium; mitochondria
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