Acamprosate Modulates Alcohol-Induced Hippocampal NMDA Receptors and Brain Microsomal Ca2+-ATPase but Induces Oxidative Stress in Rat
Acamprosate Modulates Alcohol-Induced Hippocampal NMDA Receptors and Brain Microsomal Ca2+-ATPase but Induces Oxidative Stress in Rat
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DOI：
10.1007/s00232-010-9305-y
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发表时间：
2010-09-01
影响因子：
2.4
通讯作者：
Ozcankaya, Ramazan
中科院分区：
文献类型：
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作者：
Caliskan, Ali Metehan;Naziroglu, Mustafa;Ozcankaya, Ramazan
本研究观察了阿坎酸对酒精所致大鼠脑氧化损伤、脑微粒体膜Ca ~（2+）-ATP酶（MMCA）活性及N-甲基-D-天冬氨酸受体（NMDAR）亚单位的影响。将40只雄性大鼠等分为4组。第一组作为对照，第二组接受乙醇。分别向构成第三和第四组的大鼠每天施用阿坎酸和阿坎酸加乙醇，持续21天。21天后，从四组中取出脑皮质和海马样品。酒精组脑皮质脂质过氧化（LP）水平和MMCA活性高于对照组，但谷胱甘肽过氧化物酶（GSH-Px）、维生素C、维生素E和β-胡萝卜素值低于对照组。与酒精组相比，阿坎酸组和酒精+阿坎酸组的LP水平进一步增加。与酒精组相比，阿坎酸组和酒精+阿坎酸组的GSH-Px、维生素A、维生素C、维生素E和β-胡萝卜素进一步降低。海马NMDAR 2A和2B亚基浓度在酒精组低于对照组，虽然他们增加了阿坎酸和酒精+阿坎酸。大脑皮层MMCA活性在阿坎酸组中高于酒精处理的大鼠，尽管其活性在酒精+阿坎酸组中低于阿坎酸组。在任何组中，脑皮质还原型谷胱甘肽水平均无统计学差异。氧化应激被提出来解释实验性酒精摄入的生物学副作用。阿坎酸和酒精诱导的氧化应激降低了酒精大鼠脑中的抗氧化维生素。
We investigated the effects of acamprosate on alcohol-induced oxidative toxicity, microsomal membrane Ca2+-ATPase (MMCA) activity and N-methyl-D-aspartate receptor (NMDAR) subunits in rat brain. Forty male rats were equally divided into four groups. The first group was used as control, and the second group received ethanol. Acamprosate and acamprosate plus ethanol each day were administered to rats constituting the third and fourth groups for 21 days, respectively. Brain cortical and hippocampal samples were taken from the four groups after 21 days. Brain cortical lipid peroxidation (LP) levels and MMCA activity were higher in the alcohol group than in control, although glutathione peroxidase (GSH-Px), vitamin C, vitamin E and beta-carotene values were lower in the alcohol group than in control. LP levels were further increased in the acamprosate and alcohol + acamprosate groups compared with the alcohol group. GSH-Px, vitamin A, vitamin C, vitamin E and beta-carotene in the acamprosate and alcohol + acamprosate groups were further decreased compared with the alcohol group. Hippocampal NMDAR 2A and 2B subunit concentrations were lower in the alcohol group than in control, although they were increased by acamprosate and alcohol + acamprosate. Brain cortical MMCA activity was higher in the acamprosate group than in the alcohol-treated rats, although its activity was lower in the alcohol + acamprosate group than in the acamprosate group. Brain cortical reduced glutathione levels were not found to be statistically different in any of the groups. Oxidative stress has been proposed to explain the biological side effects of experimental alcohol intake. Acamprosate and alcohol-induced oxidative stress decreased brain antioxidant vitamins in the alcoholic rats.