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标题：Effects of Manganese Complexes of Curcumin and Diacetylcurcumin on Kainic Acid-Induced Neurotoxic Responses in the Rat Hippocampus
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作者：Yaowared Sumanont ; Yukihisa Murakami ; Michihisa Tohda 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：9
页码：1732-1739
DOI：10.1248/bpb.30.1732
出版社：The Pharmaceutical Society of Japan
摘要：This study aimed to investigate the mechanism underlying the protective effects of manganese complexes of curcumin (Cp–Mn) and diacetylcurcumin (DiAc–Cp–Mn) on kainic acid (KA)-induced excitotoxicity in the rat hippocampus. Systemic injection of KA (10 mg/kg, i.p.) caused seizures and increased the expression of neurotoxic markers, immediate early genes [c- jun , cyclooxygenase 2 (COX-2), brain-derived neurotrophic factor (BDNF), and heat shock protein 70 ( hsp 70)] and a delayed response gene [inducible nitric oxide synthase ( iNOS )], which were measured at 6 and 72 h after KA injection, respectively, in the hippocampus. Pretreatment with Cp–Mn (50 mg/kg, i.p.) and DiAc–Cp–Mn (50 mg/kg, i.p.) but not with curcumin (50 mg/kg, i.p.) delayed the onset of KA-induced seizure without affecting the seizure score. KA injection induced c-Fos immunoreactivity in DG, CA1, and CA3 hippocampal regions, the expression of which peaked at 6 h after injection. Cp–Mn and DiAc–Cp–Mn treatment significantly decreased c-Fos expression elicited by KA. Moreover, Cp–Mn and DiAc–Cp–Mn administration suppressed the KA-induced expression of c- jun , COX-2 , BDNF , and iNOS mRNA, whereas curcumin attenuated only iNOS mRNA expression. No compounds tested had an effect on KA-induced hsp70 expression. It is therefore likely that in addition to radical scavenging and SOD-like activities, the suppression of potential neuronal injury marker expression by Cp–Mn and DiAc–Cp–Mn, contributes to the neuroprotective activities of these compounds, which are superior to those of curcumin, on KA-induced excitotoxicity in the hippocampus. These results suggest the beneficial effects of Cp–Mn, and DiAc–Cp–Mn on the treatment of excitotoxicity-induced neurodegenerative diseases.
关键词：curcumin manganese complex;kainic acid-induced excitotoxicity;seizure;immediate early gene