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《Anhui Medical and Pharmaceutical Journal》 2008-02
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The effects of chlorpromazine and nimodipine on neurotoxicity induced by manganese in rats

XU Dong-hui,FENG Wan-yu(Clinical Pharmacology Laboratory,First Affiliated Hospital of China Medical University,Shenyang 110001,China)  
Aim To investigate the effects of manganese on the activities of glutamine synthetase(GS),phosphate activated glutaminase(PAG),Na+-K+-ATPase,Ca2+-ATPase and the content of malondialdehyde(MDA) and to observe the effect of chlorpromazine(CPZ) and nimodipine(NIMO) on manganese-induced neurotoxicity in rats.Methods The 32 Wistar rats were divided into four groups by weight at random.The first group is the control group and the second group is the manganese exposed group.The first and second groups were intraperitoneally(ip) injected with 0.9% sodium chloride.The third and fourth groups were intervention groups and were ip injected with 14.1 μmol·kg-1 of CPZ and 2.4 mmol·kg-1 of NIMO,respectively.Two hours after ip injections,the animals in the control group were subcutaneously(sc) injected with 0.9%sodium chloride,the second to forth groups were sc injected with 200 μmol·kg-1 MnCl2.The animals were injected for 4 weeks,5 days a week.At the 24h after the last injection,the activities of PAG,GS in the corpus striatum,the activities of Na+-K+-ATPase,Ca2+-ATPase and the content of MDA in cerebral cortex were determined.Results Compared with the control group,the activity of GS was significantly decreased and PAG increased in the corpus striatum,the activities of Na+-K+-ATPase and Ca2+-ATPase decreased,the content of MDA increased in cerebral cortex in the group given 200 μmol·kg-1 MnCl2.In the groups pretreated with CPZ and NIMO,the activities of GS,Na+-K+-ATPase and Ca2+-ATPase were significantly increased compared with 200 μmol·kg-1 MnCl2 group.The activity of GS was significantly decreased in the group pretreated with CPZ and the content of MDA decreased in NIMO group.Conclusion Manganese resulted in the reduction of GS,Na+-K+-ATPase,Ca2+-ATPase activities,the increase of PAG activity and MDA content.Pretreatment with CPZ and NIMO can antagonize neurotoxicity induced by manganese to a certain extent.
【Fund】: 国家自然科学基金(编号:30771834)
【CateGory Index】: R96
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