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Possible Effects of Lamotrigine on Liver of Wister Rats Exposed to Chemoconvulsion and Chronic Restraint Model

Received: 9 August 2014     Accepted: 23 August 2014     Published: 10 September 2014
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Abstract

The present study is designed to investigate the possible hepatotoxic effects of the anti-epileptic drug “lamotrigine, LTG” in adult male wister rats after picrotoxin –induced convulsions and exposure for 21 days to chronic restraint model. This was done by a trial to find out alterations in the activities of liver enzymes and some antioxidants in this model of co-morbidity. They were treated by gastric gavage with LTG [20mg/kg body wt.] for 21days. Then rats were anesthetized and dissected to remove liver and to collect blood. Selected liver enzymes [AST, ALT] and some anti-oxidant enzymes were assayed. The results indicated that the drug significantly increased the activities of glutathione peroxidase and catalase enzymes in hepatic homogenates, while it significantly decreased the level of the lipid peroxidation expressed as thiobarbituric acid-reactive substance (TBARS) in these homogenates. However, there was an elevation of tested liver enzymes ALT & AST at the end of 21 days. This revealed the occurrence of possible hepatocellular damage. The present study recommends a regular liver function and drug monitoring during the therapeutic use of this drug in epilepsy-stress co-morbidity.

Published in American Journal of Psychiatry and Neuroscience (Volume 2, Issue 4)
DOI 10.11648/j.ajpn.20140204.11
Page(s) 50-55
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2014. Published by Science Publishing Group

Keywords

Lamotrigine, Picrotoxin, Chronic Restraint Model, Liver, Rats

References
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[7] Overstreet, K., Costanza, C., Behling, C.,Hassanin, T. and Masliah, E. (2002). Fatal progressive hepatic necrosis associated with lamotrigine treatment: A case report and literature review. Dig. Dis.Sci. 47, 1921-1925.
[8] Gutteridge J and Quinlan G (1983). Malondialdhyde formation from lipid peroxides in the thiobarbituric acid test: the role of lipid radicals, iron salt and metal chelators. J Appl Biochem. 1983; 5(4–5):293–299
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[15] Tufan K, Oztanir N, Ofluoglu E, Ozogul C, Uzum N, Dursun A, Pasaoglu H, Pasaoglu A. Ultrastructure protection and attenuation of lipid peroxidation after blockade of presynaptic release of glutamate by lamotrigine in experimental spinal cord injury. Neurosurg. Focus. 2008;25(5):E6
[16] Overstreet K, Costanza C, Behling C,Hassanin T and Masliah E. Fatal progressive hepatic necrosis associated with lamotrigine treatment: A case report and literature review. Dig. Dis.Sci.2002; 47, 1921-1925.
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    Sahar Mohamed Kamal Shams El Dine. (2014). Possible Effects of Lamotrigine on Liver of Wister Rats Exposed to Chemoconvulsion and Chronic Restraint Model. American Journal of Psychiatry and Neuroscience, 2(4), 50-55. https://doi.org/10.11648/j.ajpn.20140204.11

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    ACS Style

    Sahar Mohamed Kamal Shams El Dine. Possible Effects of Lamotrigine on Liver of Wister Rats Exposed to Chemoconvulsion and Chronic Restraint Model. Am. J. Psychiatry Neurosci. 2014, 2(4), 50-55. doi: 10.11648/j.ajpn.20140204.11

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    AMA Style

    Sahar Mohamed Kamal Shams El Dine. Possible Effects of Lamotrigine on Liver of Wister Rats Exposed to Chemoconvulsion and Chronic Restraint Model. Am J Psychiatry Neurosci. 2014;2(4):50-55. doi: 10.11648/j.ajpn.20140204.11

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  • @article{10.11648/j.ajpn.20140204.11,
      author = {Sahar Mohamed Kamal Shams El Dine},
      title = {Possible Effects of Lamotrigine on Liver of Wister Rats Exposed to Chemoconvulsion and Chronic Restraint Model},
      journal = {American Journal of Psychiatry and Neuroscience},
      volume = {2},
      number = {4},
      pages = {50-55},
      doi = {10.11648/j.ajpn.20140204.11},
      url = {https://doi.org/10.11648/j.ajpn.20140204.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajpn.20140204.11},
      abstract = {The present study is designed to investigate the possible hepatotoxic effects of the anti-epileptic drug “lamotrigine, LTG” in adult male wister rats after picrotoxin –induced convulsions and exposure for 21 days to chronic restraint model. This was done by a trial to find out alterations in the activities of liver enzymes and some antioxidants in this model of co-morbidity. They were treated by gastric gavage with LTG [20mg/kg body wt.] for 21days. Then rats were anesthetized and dissected to remove liver and to collect blood. Selected liver enzymes [AST, ALT] and some anti-oxidant enzymes were assayed. The results indicated that the drug significantly increased the activities of glutathione peroxidase and catalase enzymes in hepatic homogenates, while it significantly decreased the level of the lipid peroxidation expressed as thiobarbituric acid-reactive substance (TBARS) in these homogenates. However, there was an elevation of tested liver enzymes ALT & AST at the end of 21 days. This revealed the occurrence of possible hepatocellular damage. The present study recommends a regular liver function and drug monitoring during the therapeutic use of this drug in epilepsy-stress co-morbidity.},
     year = {2014}
    }
    

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    AU  - Sahar Mohamed Kamal Shams El Dine
    Y1  - 2014/09/10
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    T2  - American Journal of Psychiatry and Neuroscience
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    AB  - The present study is designed to investigate the possible hepatotoxic effects of the anti-epileptic drug “lamotrigine, LTG” in adult male wister rats after picrotoxin –induced convulsions and exposure for 21 days to chronic restraint model. This was done by a trial to find out alterations in the activities of liver enzymes and some antioxidants in this model of co-morbidity. They were treated by gastric gavage with LTG [20mg/kg body wt.] for 21days. Then rats were anesthetized and dissected to remove liver and to collect blood. Selected liver enzymes [AST, ALT] and some anti-oxidant enzymes were assayed. The results indicated that the drug significantly increased the activities of glutathione peroxidase and catalase enzymes in hepatic homogenates, while it significantly decreased the level of the lipid peroxidation expressed as thiobarbituric acid-reactive substance (TBARS) in these homogenates. However, there was an elevation of tested liver enzymes ALT & AST at the end of 21 days. This revealed the occurrence of possible hepatocellular damage. The present study recommends a regular liver function and drug monitoring during the therapeutic use of this drug in epilepsy-stress co-morbidity.
    VL  - 2
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Author Information
  • Department of Pharmacology, Faculty of Medicine, University of Ain-Shams, Cairo, Egypt

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