Detection of salicylate and its hydroxylated adduct 2,3-dihydroxybenzoic acid in glutamate neurotoxicity and the effects of verapamil and ryanodine in rats

Gepdiremen A. A. , singh g., MARSDEN C.

FUNDAMENTAL & CLINICAL PHARMACOLOGY, vol.14, no.1, pp.19-24, 2000 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 14 Issue: 1
  • Publication Date: 2000
  • Doi Number: 10.1111/j.1472-8206.2000.tb00389.x
  • Page Numbers: pp.19-24


It has been suggested that salicylate hydroxylation can be used to detect hydroxyl radical formation in vivo. In the present study we investigated the effects of verapamil and/or ryanodine on salicylate (SA) and its hydroxylated adduct; 2,3-dihydroxybenzoic acid (2,3-DHBA) levels in glutamate induced neurotoxicity of whole rat brains. To detect SA and 2,3-DHBA, an HPLC-EC/UV method was used. Retention time was found to be 3.9 min for 2,3-DHBA and 12.0 min for SA. Verapamil at 10(-5) and 10(-7) and ryanodine at 10(-5) M concentrations were found to have a significant decreasing effect on this degradation induced by glutamate. This was the highest dose for ryanodine tested. As an L-type voltage dependent calcium channel blocker, verapamil was found ineffective at 10(-4), 10(-6) and 10(-8) M concentrations. Surprisingly, none of the combined application groups (verapamil + ryanodine) was found effective on SA hydroxylation. As a result, ryanodine was effective only at the highest dose, while verapamil exerts its effect in a dose dependent fashion as reported before in the literature. (C) 2000 Editions scientifiques et medicales Elsevier SAS.