α-Lipoic acid alleviates pentetrazol-induced neurological deficits and behavioral dysfunction in rats with seizures via an Nrf2 pathway

被引:14
作者
Cheng, Yahong [1 ]
Luo, Fei [1 ]
Zhang, Qianying [1 ]
Sang, Ying [1 ]
Chen, Xiaofang [1 ]
Zhang, Lu [1 ]
Liu, Yonggang [1 ]
Li, Xiaofei [1 ]
Li, Jian [1 ]
Ding, Hong [1 ]
Mei, Yunqing [2 ,3 ]
机构
[1] Wuhan Univ, Sch Pharmaceut Sci, Minist Educ, Key Lab Combinatorial Biosynth & Drug Discovery, Wuhan, Hubei, Peoples R China
[2] Tongji Univ, Sch Med, Dept Cardiothorac Surg, Shanghai, Peoples R China
[3] Hubei Univ Med, Dept Cardiothorac Surg, Xiangyang Peoples Hosp 1, Shiyan, Hubei, Peoples R China
关键词
OXIDATIVE STRESS INJURY; STATUS EPILEPTICUS; CEREBRAL-CORTEX; SIGNAL PATHWAY; KAINIC ACID; HIPPOCAMPUS; EPILEPSY; ACTIVATION; BRAIN; DAMAGE;
D O I
10.1039/c7ra11491e
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Epilepsy (EP) is a type of chronic brain disease characterized by transient central nervous system malfunction which is the result of neuron paradoxical discharge in the brain. In a recent study, we evaluated the neuroprotective effect of a-lipoic acid on pentetrazol-induced rats. Epileptic rats were induced by intraperitoneal injection of pentetrazol (35 mg kg(-1)), and were intragastrically administered with alpha-lipoic acid for a month. The treatment with alpha-lipoic acid significantly reduced the total frequency of epileptic seizures and improved the behavior impairment and cognitive disorder caused by pentetrazol toxicity. With the administration of alpha-lipoic acid, not only did the apoptosis rate of nerve cells decrease, but also the formation of nitric oxide and malondialdehyde was inhibited. We also recorded evidence suggesting the treatment of alpha-lipoic acid could enhance the activity of antioxidant enzymes. Furthermore, in the hippocampus area of the brain, alpha-lipoic acid treatment promoted the translocation of Nrf2 in the nuclear fraction and increased the expression of HO-1 and NQO1. Our data indicated that alpha-lipoic acid may be a potential candidate for lessening the number of epileptic attacks, improving the behavior and cognitive disorder and cutting down the apoptosis rate of nerve cells in a pentetrazol-induced rat model through activating the Nrf2 signaling pathway.
引用
收藏
页码:4084 / 4092
页数:9
相关论文
共 48 条
[31]   Mitochondrial respiration deficits driven by reactive oxygen species in experimental temporal lobe epilepsy [J].
Rowley, Shane ;
Liang, Li-Ping ;
Fulton, Ruth ;
Shimizu, Takahiko ;
Day, Brian ;
Patel, Manisha .
NEUROBIOLOGY OF DISEASE, 2015, 75 :151-158
[32]   Oxidative stress, metalloproteinase and LDH in children with intractable and non-intractable epilepsy as reflected in salivary analysis [J].
Shahar, Eli ;
Attias, Uri ;
Savulescu, Dana ;
Genizin, Jacob ;
Gavish, Moshe ;
Nagler, Rafael .
EPILEPSY RESEARCH, 2014, 108 (01) :117-124
[33]   Cap-independent Nrf2 translation is part of a lipoic acid-stimulated detoxification stress response [J].
Shay, Kate Petersen ;
Michels, Alexander J. ;
Li, Wenge ;
Kong, Ah-Ng Tony ;
Hagen, Tory M. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2012, 1823 (06) :1102-1109
[34]   Hippocampal injury-induced cognitive and mood dysfunction, altered neurogenesis, and epilepsy: Can early neural stem cell grafting intervention provide protection? [J].
Shetty, Ashok K. .
EPILEPSY & BEHAVIOR, 2014, 38 :117-124
[35]   Antagomirs Targeting MiroRNA-134 Attenuates Epilepsy in Rats through Regulation of Oxidative Stress, Mitochondrial Functions and Autophagy [J].
Sun, Jiahang ;
Gao, Xiaoying ;
Meng, Dawei ;
Xu, Yang ;
Wang, Xichun ;
Gu, Xin ;
Guo, Mian ;
Shao, Xiaodong ;
Yan, Hongwen ;
Jiang, Chuanlu ;
Zheng, Yongri .
FRONTIERS IN PHARMACOLOGY, 2017, 8
[36]  
Sun MY, 2015, INT J CLIN EXP PATHO, V8, P14701
[37]   Longitudinal course of epilepsy in Rett syndrome and related disorders [J].
Tarquinio, Daniel C. ;
Hou, Wei ;
Berg, Anne ;
Kaufmann, Walter E. ;
Lane, Jane B. ;
Skinner, Steven A. ;
Motil, Kathleen J. ;
Neul, Jeffrey L. ;
Percy, Alan K. ;
Glaze, Daniel G. .
BRAIN, 2017, 140 (02) :306-318
[38]   A rare cause of status epilepticus; alpha lipoic acid intoxication, case report and review of the literature [J].
Tolunay, Orkun ;
Celik, Tamer ;
Komur, Mustafa ;
Gezgin, Ali Emre ;
Kaya, Musa Soner ;
Celik, Umit .
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY, 2015, 19 (06) :730-732
[39]   Resveratrol lacks protective activity against acute seizures in mouse models [J].
Tomaciello, Francesca ;
Leclercq, Karine ;
Kaminski, Rafal M. .
NEUROSCIENCE LETTERS, 2016, 632 :199-203
[40]   Role of α-lipoic acid in dextran sulfate sodium-induced ulcerative colitis in mice: Studies on inflammation, oxidative stress, DNA damage and fibrosis [J].
Trivedi, P. P. ;
Jena, G. B. .
FOOD AND CHEMICAL TOXICOLOGY, 2013, 59 :339-355