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ω-3脂肪酸、锂和阿立哌唑联合使用可降低躁狂小鼠大脑中的氧化应激。

Combination of omega-3 Fatty acids, lithium, and aripiprazole reduces oxidative stress in brain of mice with mania.

作者信息

Arunagiri Pandiyan, Rajeshwaran Krishnamoorthy, Shanthakumar Janakiraman, Tamilselvan Thangavel, Balamurugan Elumalai

机构信息

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, 608 002, India.

出版信息

Biol Trace Elem Res. 2014 Sep;160(3):409-17. doi: 10.1007/s12011-014-0067-8. Epub 2014 Jul 18.

Abstract

Manic episode in bipolar disorder (BD) was evaluated in the present study with supplementation of omega-3 fatty acids in combination with aripiprazole and lithium on methylphenidate (MPD)-induced manic mice model. Administration of MPD 5 mg/kg bw intraperitoneally (i.p.) caused increase in oxidative stress in mice brain. To retract this effect, supplementation of omega-3 fatty acids 1.5 ml/kg (p.o.), aripiprazole 1.5 mg/kg bw (i.p.), and lithium 50 mg/kg bw (p.o) were given to mice. Omega-3 fatty acids alone and in combination with aripiprazole- and lithium-treated groups significantly reduced the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation products (thiobarbituric acid reactive substances) in the brain. MPD treatment significantly decreased the reduced glutathione (GSH) level and glutathione peroxidase (GPx) activity, and they were restored by supplementation of omega-3 fatty acids with aripiprazole and lithium. There is no remarkable difference in the effect of creatine kinase (CK) activity between MPD-induced manic model and the treatment groups. Therefore, our results demonstrate that oxidative stress imbalance and mild insignificant CK alterations induced by administration of MPD can be restored back to normal physiological levels through omega-3 fatty acids combined with lithium and aripiprazole that attributes to effective prevention against mania in adult male Swiss albino mice.

摘要

在本研究中,对双相情感障碍(BD)的躁狂发作进行了评估,采用在哌醋甲酯(MPD)诱导的躁狂小鼠模型中补充ω-3脂肪酸,并联合阿立哌唑和锂盐的方法。腹腔注射(i.p.)5mg/kg体重的MPD会导致小鼠大脑氧化应激增加。为了抵消这种影响,给小鼠口服1.5ml/kg的ω-3脂肪酸(p.o.)、腹腔注射1.5mg/kg体重的阿立哌唑(i.p.)以及口服50mg/kg体重的锂盐(p.o.)。单独使用ω-3脂肪酸以及与阿立哌唑和锂盐联合治疗的组均显著降低了大脑中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和脂质过氧化产物(硫代巴比妥酸反应性物质)的水平。MPD治疗显著降低了还原型谷胱甘肽(GSH)水平和谷胱甘肽过氧化物酶(GPx)活性,而补充ω-3脂肪酸联合阿立哌唑和锂盐可使其恢复。MPD诱导的躁狂模型与治疗组之间肌酸激酶(CK)活性的影响没有显著差异。因此,我们的结果表明,通过ω-3脂肪酸联合锂盐和阿立哌唑,可将MPD给药引起的氧化应激失衡和轻度不显著的CK改变恢复到正常生理水平,这有助于有效预防成年雄性瑞士白化小鼠的躁狂发作。

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