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Brain Sci. 2018, 8(3), 45; https://doi.org/10.3390/brainsci8030045

l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70

1
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
2
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
3
Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
4
Neuroimaging Research Branch, IRP, National Institute on Drug Abuse, National Institutes of Health, Biomedical Research Center, 251 Bayview Blvd, Baltimore, MD 21224, USA
*
Author to whom correspondence should be addressed.
Received: 30 January 2018 / Revised: 3 March 2018 / Accepted: 9 March 2018 / Published: 14 March 2018
(This article belongs to the Special Issue Diagnosis and Surgical Treatment of Epilepsy)
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Abstract

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. View Full-Text
Keywords: l-carnitine; PTZ; epilepsy; apoptosis; β-catenin; oxidative stress l-carnitine; PTZ; epilepsy; apoptosis; β-catenin; oxidative stress
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Hussein, A.M.; Adel, M.; El-Mesery, M.; Abbas, K.M.; Ali, A.N.; Abulseoud, O.A. l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70. Brain Sci. 2018, 8, 45.

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