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

• Published in: Brain research Vol. 1686; pp. 1 - 9
• Main Authors: Lakatos, Renáta Krisztina, Dobolyi, Árpád, Kovács, Zsolt
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2018
• Subjects: Absence epilepsy; Allopurinol; Allopurinol - pharmacology; Animals; Anticonvulsants - pharmacology; Brain - drug effects; Brain - physiopathology; Cyclooxygenase Inhibitors - pharmacology; Disease Models, Animal; Electroencephalography - methods; Epilepsy, Absence - chemically induced; Epilepsy, Absence - physiopathology; Indomethacin; Inosine; Male; Rats, Wistar; Uric acid; Uric Acid - pharmacology; WAG/Rij rats; PGE2; SWD; IL-1; Absence epilepsy; EEG; Allopurinol; CNS; WAG/Rij; i.p; WAG/Rij rats; Uric acid; IMP; GABAAR; Inosine; Indomethacin; A2AR; COX-1 and COX-2
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2018.02.012

•I.p. injected uric acid (UA) increased the number of spike-wave discharges (SWDs).•Allopurinol also elevated the SWD number in Wistar Albino Glaxo/Rijswijk/WAG/Rij rats.•Injection of allopurinol with inosine and inosine with UA enhanced the SWD number.•Application of indomethacin with UA abolished the UA-evoked increase in SWD number.•Both uric acid and allopurinol have proepileptic effects at least in WAG/Rij rats. 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. 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.