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Ben-Cherif W, Dridi I, Aouam K, et al. Chronotolerance study of the antiepileptic drug valproic acid in mice. J Circadian Rhythms. 2012;10:3doi: 10.1186/1740-3391-10-3.
Ben-Cherif, W., Dridi, I., Aouam, K., Ben-Attia, M., Reinberg, A., & Boughattas, N. A. (2012). Chronotolerance study of the antiepileptic drug valproic acid in mice. Journal of circadian rhythms, 103. https://doi.org/10.1186/1740-3391-10-3
Ben-Cherif, Wafa, et al. "Chronotolerance study of the antiepileptic drug valproic acid in mice." Journal of circadian rhythms vol. 10 (2012): 3. doi: https://doi.org/10.1186/1740-3391-10-3
Ben-Cherif W, Dridi I, Aouam K, Ben-Attia M, Reinberg A, Boughattas NA. Chronotolerance study of the antiepileptic drug valproic acid in mice. J Circadian Rhythms. 2012 May 10;10:3. doi: 10.1186/1740-3391-10-3. PMID: 22574933; PMCID: PMC3431278.
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J Circadian Rhythms. 2012 May 10;10:3. doi: 10.1186/1740-3391-10-3.

Chronotolerance study of the antiepileptic drug valproic acid in mice.

Journal of circadian rhythms

Wafa Ben-Cherif, Ichrak Dridi, Karim Aouam, Mossadok Ben-Attia, Alain Reinberg, Naceur A Boughattas

Affiliations

  1. Laboratoire de Pharmacologie, Faculté de Médecine, Université de Monastir, Monastir, Tunisia. [email protected].

PMID: 22574933 PMCID: PMC3431278 DOI: 10.1186/1740-3391-10-3

Abstract

BACKGROUND: Valproic acid (VPA) is an antiepileptic drug widely used for the treatment of absence seizures and generalized tonic-clonic seizures. The present work aims to study whether VPA-induced toxicity varies according to the dosing-time in the 24 hour-scale.

METHODS: The influence of dosing-time on tolerance to VPA was investigated in 120 male Swiss mice synchronized under a light-dark cycle (12:12). The mean VPA lethal dose was first determined to be 850 ± 0.2 mg/kg, i.p.. Such a dose was administered by i.p. route to a total of 90 mice divided in six circadian stages [1, 5, 9, 13, 17 and 21 Hours After Light Onset (HALO)] (15 mice/circadian time); 30 mice were used as control (5 mice / circadian time).

RESULTS: The surviving treated mice exhibited a significant circadian variation in rectal temperature and body weight loss (p < 0.001). The least rectal temperature change and body weight loss occurred when VPA was injected at 9 HALO. Drug dosing at 9 HALO resulted in -9 % weight loss whereas drug dosing at 17 HALO was -15 % (Ø = 20.3 HALO ± 1.1 h, p ≤ 0.0001). Lethal toxicity also varied according to circadian dosing-time (χ2 = 42.1, p < 0.0001). The highest (60 %) and the lowest (6.67 %) survival rates were observed at 9 HALO and 17 HALO respectively. Cosinor analyses validated a significant circadian rhythm in survival duration with an acrophase at 8.4 HALO ± 0.75 h (p < 0.001).

CONCLUSIONS: With regards to these data the optimal tolerance to VPA occurred when the drug was administered in the second half of the light-rest span of mice which is physiologically analogous to the second half of the night for human patients.

References

  1. Epilepsy Behav. 2009 Nov;16(3):461-7 - PubMed
  2. Trends Pharmacol Sci. 2009 Oct;30(10):509-14 - PubMed
  3. Chronobiol Int. 2003 Nov;20(6):1103-16 - PubMed
  4. Psychoneuroendocrinology. 2000 Jul;25(5):519-34 - PubMed
  5. Epilepsy Res. 2000 Nov;42(1):43-55 - PubMed
  6. Pharmacol Res. 1996 Feb;33(2):107-15 - PubMed
  7. J Clin Neurophysiol. 2011 Apr;28(2):146-53 - PubMed
  8. J Pharmacol Sci. 2007 Feb;103(2):155-8 - PubMed
  9. Life Sci. 1997;60(22):1933-42 - PubMed
  10. Jpn J Pharmacol. 1988 May;47(1):11-9 - PubMed
  11. Eur J Cancer Clin Oncol. 1985 Oct;21(10):1245-51 - PubMed
  12. Neurology. 2000 Jul 12;55(1):150-1 - PubMed
  13. Epilepsy Res. 2001 Nov;47(1-2):155-74 - PubMed
  14. Am Rev Respir Dis. 1993 Jun;147(6 Pt 2):S2-19 - PubMed
  15. Brain Dev. 2008 Apr;30(4):279-86 - PubMed
  16. J Nutr. 1975 Feb;105(2):171-84 - PubMed
  17. J Circadian Rhythms. 2011 Jun 17;9(1):5 - PubMed
  18. CNS Drugs. 2002;16(10):695-714 - PubMed
  19. Cancer Res. 1989 Jun 15;49(12):3362-8 - PubMed
  20. Psychopharmacol Bull. 2003;37 Suppl 2:17-24 - PubMed
  21. J Affect Disord. 2010 Aug;124(3):319-23 - PubMed
  22. Chronobiol Int. 2004 Jan;21(1):161-70 - PubMed
  23. Jpn J Pharmacol. 1996 Mar;70(3):253-8 - PubMed
  24. Br J Pharmacol. 2006 Oct;149(3):250-60 - PubMed
  25. Epilepsy Behav. 2008 Oct;13(3):438-44 - PubMed
  26. Chronobiologia. 1979 Oct-Dec;6(4):305-23 - PubMed
  27. Seizure. 2010 Dec;19(10):650-5 - PubMed
  28. Epilepsy Res. 1992 Sep;12(3):199-205 - PubMed
  29. Biol Rhythm Res. 2007;38(4):275-325 - PubMed
  30. Emerg Med J. 2007 Sep;24(9):677-8 - PubMed
  31. Neurosci Lett. 1993 Feb 5;150(1):112-6 - PubMed
  32. Eur J Pharmacol. 1995 Oct 6;293(3):281-5 - PubMed
  33. Cell. 1997 Dec 12;91(6):855-60 - PubMed
  34. Annu Rev Pharmacol Toxicol. 1992;32:51-66 - PubMed
  35. Pathol Biol (Paris). 2003 Jun;51(4):185-90 - PubMed
  36. Epilepsy Res. 2009 Jul;85(1):96-106 - PubMed

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