Stabilization of mitochondrial function by tetramethylpyrazine protects against kainate-induced oxidative lesions in the rat hippocampus.
Mitochondria are critical regulators of cell death, a key feature of neurodegeneration. Reactive oxygen species (ROS) are crucial to Ca(2+)-mediated effects of glutamate receptor activation leading to neuronal degeneration. Tetramethylpyrazine (TMP) is a principal ingredient of Ligusticum wallichi Franchat (a Chinese herb), used for treatment of cardiovascular and cerebrovascular ischemic diseases. However, its protection against oxidative brain injury associated with excessive activation of glutamate receptors is unknown. In this study, we demonstrate TMP neuroprotection against kainate-induced excitotoxicity in vitro and in vivo. We found that TMP could partly alleviate kainate-induced status epilepticus in rats and prevented and rescued neuronal loss in the hippocampal CA3 but not the CA1 region. The partial prevention and rescue of neuronal loss by TMP were attributable to the preservation of the structural and functional integrity of mitochondria, evidenced by maintaining the mitochondrial membrane potential, ATP production, and complex I and III activities. Stabilization of mitochondrial function was linked to the observation that TMP could function as a reductant/antioxidant to quench ROS, block lipid peroxidation, and protect enzymatic antioxidants such as glutathione peroxidase and glutathione reductase. These results suggest that TMP may protect against oxidative brain injury by stabilization of mitochondrial function through quenching of ROS.
Li
Shu-Yan
SY
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, People's Republic of China. shuyanli@bjmu.edu.cn
Jia
Yu-Hong
YH
Sun
Wen-Ge
WG
Tang
Yuan
Y
An
Guo-Shun
GS
Ni
Ju-Hua
JH
Jia
Hong-Ti
HT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D008516:Medicine, Chinese Traditional; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000473:pathology; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D018690:Excitatory Amino Acid Agonists; D010936:Plant Extracts; D011719:Pyrazines; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D007608:Kainic Acid; D002118:Calcium; C017953:tetramethylpyrazine