Genistein attenuates oxidative stress and neuronal damage following transient global cerebral ischemia in rat hippocampus.
Oxidative stress is believed to contribute to neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. The present study was undertaken to evaluate the possible antioxidant neuroprotective effect of genistein against neuronal death in hippocampal CA1 neurons following transient global cerebral ischemia in the rat. Transient global cerebral ischemia was induced in male Sprague-Dawley rats by four-vessel-occlusion for 10min. At various times of reperfusion, the histopathological changes and the levels of mitochondria-generated reactive oxygen species (ROS), malondialdehyde (MDA), cytosolic cytochrome c and caspase-3 activity in hippocampus were measured. We found extensive neuronal death in the CA1 region at day 5 after I/R. The ischemic changes were preceded by increases in ROS generation and MDA concentration and followed by increased cytosolic cytochrome c, and subsequently caspase-3 activation and apoptosis. Treatment with genistein (15mg/kg, i.p.) significantly attenuated ischemia-induced neuronal death. Genistein administration also decreased ROS generation, MDA concentration and the apoptotic indices. These results suggest that genistein protects neurons from transient global cerebral I/R injury in rat hippocampus by attenuating oxidative stress, lipid peroxidation and the signaling cascade leading to apoptotic cell death.
Liang
Hua-Wei
HW
Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Qiu
Shui-Feng
SF
Shen
Jia
J
Sun
Li-Na
LN
Wang
Jing-Ye
JY
Bruce
Iain C
IC
Xia
Qiang
Q
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D019833:Genistein / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D000975:Antioxidants; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D045304:Cytochromes c; D019833:Genistein; D053148:Caspase 3