Uric acid and allopurinol aggravate absence epileptic activity in Wistar Albino Glaxo Rijswijk rats

Renáta Krisztina Lakatos, Árpád Dobolyi, Zsolt Kovács
  • Brain Research, May 2018, Elsevier
  • DOI: 10.1016/j.brainres.2018.02.012

Uric acid and allopurinol aggravate absence epileptic activity

What is it about?

Uric acid has a role in several physiological and pathophysiological processes. For example, uric acid may facilitate seizure generalization while reducing uric acid level may evoke anticonvulsant/antiepileptic effects. Allopurinol blocks the activity of xanthine oxidase, by which allopurinol inhibits catabolism of hypoxanthine to xanthine and uric acid and, as a consequence, decreases the level of uric acid. Although the modulation of serum uric acid level is a widely used strategy in the treatment of certain diseases, our knowledge regarding the effects of uric acid on epileptic activity is far from complete. Thus, the main aim of this study was the investigation of the effect of uric acid on absence epileptic seizures (spike-wave discharges: SWDs) in a model of human absence epilepsy, the Wistar Albino Glaxo/Rijswijk (WAG/Rij) rat. We investigated the influence of intraperitoneally (i.p.) injected uric acid (100 mg/kg and 200 mg/kg), allopurinol (50 mg/kg and 100 mg/kg), a cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibitor indomethacin (10 mg/kg) and inosine (500 mg/kg) alone and the combined application of allopurinol (50 mg/kg) with uric acid (100 mg/kg) or inosine (500 mg/kg) as well as indomethacin (10 mg/kg) with uric acid (100 mg/kg) and inosine (500 mg/kg) with uric acid (100 mg/kg) on absence epileptic activity.

Why is it important?

We demonstrated that both uric acid and allopurinol alone significantly increased the number of SWDs whereas indomethacin abolished the uric acid-evoked increase in SWD number. Our results suggest that uric acid and allopurinol have proepileptic effects in WAG/Rij rats.


Dr Zsolt Kovacs (Author)
Eötvös Loránd University

As an increase of blood uric acid level in patients with absence epilepsy may aggravate epileptic seizures, continuous monitoring of their blood uric acid level, and maintaining it within the normal range could be beneficial. Moreover, combination of allopurinol with other drugs may intensify the absence epileptic activity and, potentially, modulate/decrease the effectivity of antiepileptic drugs in absence epileptic patients. Thus, usability of allopurinol for the treatment of human absence epilepsy is highly questionable.

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The following have contributed to this page: Dr Zsolt Kovacs