l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70.
l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70.
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DOI：
10.3390/brainsci8030045
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发表时间：
2018-03-14
期刊：
影响因子：
3.3
通讯作者：
Abulseoud OA
中科院分区：
文献类型：
--
作者：
Hussein AM;Adel M;El-Mesery M;Abbas KM;Ali AN;Abulseoud OA
左旋肉碱是一种独特的运动员营养补充剂，最近被研究为某些神经精神疾病的潜在治疗方法。然而，其在控制癫痫发作方面的功效尚未得到研究。Sprague道利大鼠随机分配接受生理盐水（Sal）（阴性对照）或戊四唑（PTZ）40 mg/kg i. p. × 3次/周× 3周。PTZ组又分为两组，第一组口服左旋卡尼汀（l-Car）（100 mg/kg/d × 4周）（PTZ + l-Car），第二组口服生理盐水（PTZ + Sal）。对每只动物的癫痫发作评分、至首次癫痫发作的时间和癫痫发作持续时间进行每日鉴别和定量。在动物脑中检查分子氧化标记物。l-Car治疗与癫痫发作评分显著降低相关（p = 0.0002），早在治疗第2天就显示了这一点，并在整个治疗期间持续存在。此外，l-Car显著延长首次癫痫发作的时间（p < 0.0001）和缩短癫痫发作持续时间（p = 0.028）。此外，l-Car给药4周减弱了PTZ诱导的氧化应激标志物丙二醛（MDA）水平的增加（p < 0.0001），降低了过氧化氢酶的活性（p = 0.0006），增加了抗氧化剂GSH的活性（p < 0.0001）。此外，l-Car显著降低PTZ诱导的caspase-3（p < 0.0001）和β-连环蛋白（p < 0.0001）蛋白表达的升高。总的来说，我们的研究结果表明，潜在的治疗作用的l-Car在癫痫发作控制，并要求测试这些临床前结果的概念试点临床研究的证据。
l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal) (negative control) or pentylenetetrazole (PTZ) 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car) (100 mg/kg/day × 4 weeks) (PTZ + l-Car), while the second group received saline (PTZ + Sal). Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score (p = 0.0002) that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure (p < 0.0001) and shortened seizure duration (p = 0.028). In addition, l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA) (p < 0.0001) and reduced the activity of catalase enzyme (p = 0.0006) and increased antioxidant GSH activity (p < 0.0001). Moreover, l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 (p < 0.0001) and β-catenin (p < 0.0001). Overall, our results suggest a potential therapeutic role of l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.
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DOI：
10.1016/s0169-328x(96)00138-6
发表时间：
1997-05-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Foster, JA;Brown, IR
通讯作者：
Brown, IR
影响因子：
3.3
作者：
GASS, P;PRIOR, P;KIESSLING, M
通讯作者：
KIESSLING, M
影响因子：
6.1
作者：
Kanitkar, Meghana;Bhonde, Ramesh R.
通讯作者：
Bhonde, Ramesh R.
影响因子：
3.3
作者：
Dericioglu, N.;Soylemezoglu, F.;Dalkara, T.
通讯作者：
Dalkara, T.
影响因子：
3.3
作者：
Goodenough, S;Schleusner, D;Behl, C
通讯作者：
Behl, C