PDF herunterladen
CC BY-NC-ND 4.0 · International Journal of Epilepsy 2017; 04(02): 119-124
DOI: 10.1016/j.ijep.2017.07.001
Clinical Study
Thieme Medical and Scientific Publishers Private Ltd.

Taurine supplementation to anti-seizure drugs as the promising approach to treat pharmacoresistant epilepsy: A pre-clinical study

Sandeep Kumar
1   Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala, India
,
Rajesh Kumar Goel
1   Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala, India
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 26. Februar 2017

Accepted: 20. Juli 2017

Publikationsdatum:
06. Mai 2018 (online)

   Lizenzen und Reprints

Abstract

Background Pharmacoresistance leads to severe, irreversible disabilities and premature death in ∼30% cases of epilepsy despite adequate and appropriate treatment with available anti-seizure drugs (ASDs) without any underlying cause. In light of the large body of evidence which suggests the anti-seizure action of taurine in experimental animals and its wide safety margins in human, supplementation of this inhibitory amino-sulfonic acid to available ASDs seems promising to treat pharmacoresistant epilepsy.

Methods We examined the anti-seizure effect of lamotrigine (15 mg/kg), levetiracetam (40 mg/kg), carbamazepine (40 mg/kg), phenytoin (35 mg/kg) & taurine (50, 100 & 200 mg/kg) in lamotrigine pre-treated pentylenetetrazole-kindled mice (LPK) which mimic core features of pharmacoresistant epilepsy, either alone ASDs or in combinations whereby three different doses of taurine were supplemented with tested ASDs.

Results Both, the ASDs and the taurine were failed to suppress generalized tonic-clonic seizures in LPK mice. However, taurine supplementation clearly restored the anti-seizure effect of tested ASDs. Further neurochemical studies revealed that higher levels of taurine in the hippocampus and cerebral cortex restored the imbalance between major excitatory neurotransmitters glutamate & its inhibitory counterpart GABA.

Conclusions These findings emphasize that supplementation of taurine with ASDs may be useful to treat pharmacoresistant epilepsy. Thus, further clinical validation is encouraged.

Keywords

Epilepsy - Kindling - Lamotrigine - Pharmacoresistant - Supplementation - Taurine
 

  • References

  • 1 Brodie MJ. Pharmacological treatment of drug-resistant epilepsy in adults: a practical guide. Curr Neurol Neurosci Rep 16 2016; 82
    CrossrefPubMedGoogle Scholar
  • 2 Jette N, Engel JJ. Refractory epilepsy is a life-threatening disease: lest we forget. Neurology 86 2016; 1932-1933
    CrossrefPubMedGoogle Scholar
  • 3 Loscher W, Klitgaard H, Twyman RE, Schmidt D. New avenues for antiepileptic drug discovery and development. Nat Rev Drug Discov 12 2013; 757-776
    CrossrefPubMedGoogle Scholar
  • 4 Engel JJ. What we do for people with drug-resistant epilepsy? The 2016 Wartenberg Lecture. Neurology 87 2016; 2483-2489
    CrossrefPubMedGoogle Scholar
  • 5 Patsalos PN. Drug interactions with the newer antiepileptic drugs (AEDs) part-1: pharmacokinetic and pharmacodynamic interactions between AEDs. Clin Pharmacokinet 52 2013; 927-966
    CrossrefPubMedGoogle Scholar
  • 6 Berg AT. Comorbidities in epilepsies: overview. Panayiotopoulos CP. Atlas of Epilepsies. 2010. Springer; London: 1321-1324
    CrossrefGoogle Scholar
  • 7 Benbadis SR. Non-pharmacological treatments for epilepsies: overview. Panayiotopoulos CP. Atlas of Epilepsies. 2010. Springer; London: 1621-1623
    CrossrefGoogle Scholar
  • 8 Goodfellow M, Rummel C, Abela E, Richardson MP, Schindler K, Terry JR. Estimation of brain network ictogenicity predicts outcome from epilepsy surgery. Sci Rep 6 2016; 29215
    CrossrefPubMedGoogle Scholar
  • 9 Gschwind M, Seeck M. Modern management of seizures and epilepsy. Swiss Med Wkly 146 2016; w14310
    PubMedGoogle Scholar
  • 10 Jobst BC, Cascino GD. Resective epilepsy surgery for drug resistant focal epilepsy: a review. JAMA 313 2015; 285-293
    CrossrefPubMedGoogle Scholar
  • 11 Bejarano E, Rodriguez-Navarro JA. Autophagy and amino acid metabolism in the brain: implications for epilepsy. Amino Acids 47 2015; 2113-2126
    CrossrefPubMedGoogle Scholar
  • 12 Szyndler J, Turzynska D, Sobolewska A. et al. Changes in the concentration of amino acids in the hippocampus of pentylenetetrazole kindled rats. Neurosci Lett 439 2008; 245-249
    CrossrefPubMedGoogle Scholar
  • 13 Van Gelder NM, Sherwin AL, Rasmussen T. Amino acids content of epileptogenic human brain: focal versus surrounding regions. Brain Res 40 1972; 385-393
    CrossrefPubMedGoogle Scholar
  • 14 Clanton RM, Wu G, Akabani G, Aramavo R. Control of seizures by ketogenic diet-induced modulation of metabolic pathways. Amino Acids 49 2017; 1-20
    CrossrefPubMedGoogle Scholar
  • 15 Ebrahimi HA, Ebrahimi S. Evaluation of charged amino acids on uncontrolled seizures. Neurol Res Int 2015 2015; 124507
    PubMedGoogle Scholar
  • 16 El ldrissi A, Trenkner E. Growth factors and taurine protect against excitotoxicity by stabilizing calcium homeostasis and energy metabolism. J Neurosci 19 1999; 9459-9468
    CrossrefPubMedGoogle Scholar
  • 17 Wu H, Jin Y, Wei J, Jin H, Sha Wu JY. Mode of action of taurine as a neuroprotector. Brain Res 1038 2005; 123-131
    CrossrefPubMedGoogle Scholar
  • 18 Jia F, Yue M, Chandra D. et al. Taurine is a potent activator of extra synaptic GABA (A) receptors in the thalamus. J Neurosci 28 2008; 106-115
    CrossrefPubMedGoogle Scholar
  • 19 Malminen O, Kontro P. Modulation of the GABA-benzodiazepine receptor complex by taurine in rat brain membranes. Neurochem Res 11 1986; 85-94
    CrossrefPubMedGoogle Scholar
  • 20 L’Amoreaux WJ, Marsillo A, El-ldrissi A. Pharmacological characterization of GABAA receptors in taurine-fed mice. J Biomed Sci 17 2010; 14
    CrossrefPubMedGoogle Scholar
  • 21 Levinskaya N, Trenkner E, El ldrissi A. Increased GAD-positive neurons in the cortex of taurine fed mice. Adv Exp Med Biol 583 2006; 411-417
    PubMedGoogle Scholar
  • 22 Joseph MH, Emson PC. Taurine and cobalt induced epilepsy in the rat: a biochemical and electrocorticographic study. J Neurochem 27 1976; 1495-1501
    CrossrefPubMedGoogle Scholar
  • 23 Lasley SM. Roles of neurotransmitter amino acids in seizure severity and experience in the genetically epilepsy prone rats. Brain Res 560 1991; 63-70
    CrossrefPubMedGoogle Scholar
  • 24 Ghandforoush sattari M, Mashayekhi S, Krishna CV, Thompson JP, Rutledge PA. Pharmacokinetics of oral taurine in healthy volunteers. J Amino Acids 2010 2010; 346237
    PubMedGoogle Scholar
  • 25 Loscher W. The search for new screening models of pharmacoresistant epilepsy: is induction of acute seizure in epileptic rodents a suitable approach?. Neurochem Res. 42 2016; 1926-1938 10.1007/s11064-016-2025-7
    PubMedGoogle Scholar
  • 26 Singh E, Pillai KK, Mehndiratta M. Characterization of a lamotrigine resistant kindled model of epilepsy in mice: evaluation of drug resistance mechanism. Basic Clin Pharmacol Toxicol 115 2014; 373-378
    CrossrefPubMedGoogle Scholar
  • 27 Srivastava AK, White HS. Carbamazepine but not valproate, displays pharmacoresistance in lamotrigine resistant amygdale kindled rats. Epilepsy Res 104 2012; 26-34
    PubMedGoogle Scholar
  • 28 Srivastava AK, Alex AB, Wilcox KS, White HS. Rapid loss of efficacy to the antiseizure drugs lamotrigine and carbamazepine: a novel experimental model of pharmacoresistant epilepsy. Epilepsia 54 2013; 1186-1194
    CrossrefPubMedGoogle Scholar
  • 29 Mishra A, Goel RK. Psychoneurochemical investigations to reveal neurobiology of memory deficit in epilepsy. Neurochem Res 38 2013; 2503-2515
    CrossrefPubMedGoogle Scholar
  • 30 Pahwa P, Goel RK. Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazole induced kindling and associated depression and memory deficit. Epilepsy Behav 57 2016; 196-201
    CrossrefPubMedGoogle Scholar
  • 31 Singh D, Mishra A, Goel RK. Effect of saponin fraction from Ficus religiosa on memory deficit, behavioural and biochemical impairments in pentylenetetrazole kindled mice. Epilepsy Behav 27 2013; 206-211
    CrossrefPubMedGoogle Scholar
  • 32 Brodie MJ, Kwan P. Pharmacological properties of antiepileptic drugs and their significance in clinical practice. Panayiotopoulos CP. Atlas of Epilepsies. 2010. Springer; London: 1425-1430
    CrossrefGoogle Scholar
  • 33 Löscher W. The pharmacokinetics of antiepileptic drugs in rats: consequences for maintaining effective drug levels during prolonged drug administration in rat models of epilepsy. Epilepsia 48 2007; 1245-1258
    CrossrefPubMedGoogle Scholar
  • 34 Markowitz GJ, Kadam SD, Boothe DM, Irving ND, Comi AM. The pharmacokinetic of commonly used antiepileptic drugs in immature CD1 mice. Neuroreport 21 2010; 452-456
    CrossrefPubMedGoogle Scholar
  • 35 Zapata A, Chefer VI, Shippensburg TS, Denoroy L. Detection and quantification of neurotransmitters in dialysates. Curr Protoc Neurosci 7 2009; 1-30
    PubMedGoogle Scholar
  • 36 Spijker S. Dissection of rodent brain regions. Li KW. Neuroproteomics. 2011. Humana Press; 13-26
    Google Scholar
  • 37 Gawande DY, Goel RK. Pharmacological validation of in-silico guided novel nootropic potential of Achyranthes aspera L. J Ethnopharmacol 175 2015; 324-334
    CrossrefPubMedGoogle Scholar
  • 38 Junyent F, Utrera J, Romero R. et al. Prevention of epilepsy by taurine treatments in mice experimental model. J Neurosci Res 87 2009; 1500-1508
    CrossrefPubMedGoogle Scholar
  • 39 Li Z, Yamamoto Y, Morimoto T, Ono J, Okada S, Yamatodni A. The effect of pentylenetetrazole kindling on extracellular glutamate and taurine levels in the frontal cortex of rats. Neurosci 282 2000; 117-119
    PubMedGoogle Scholar
  • 40 Rogawski MA. The intrinsic severity hypothesis of pharmacoresistance to antiepileptic drugs. Epilepsia 54 2013; 33-40
    PubMedGoogle Scholar