Detection of salicylate and its hydroxylated adduct 2,3-dihydroxybenzoic acid in glutamate neurotoxicity and the effects of verapamil and ryanodine in rats.
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.
Gepdiremen
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A
Department of Pharmacology, Medical Faculty, Atatürk University, Erzurum, Turkey. akcahan@atauni.edu.tr
Singh
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G
Marsden
C A
CA
D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018698:Glutamic Acid / Q000633:toxicity*; D062385:Hydroxybenzoates / Q000097:blood / Q000378:metabolism*; D008297:Male; D020258:Neurotoxicity Syndromes / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology*; D012459:Salicylates / Q000097:blood / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D062385:Hydroxybenzoates; D012459:Salicylates; D012433:Ryanodine; D018698:Glutamic Acid; C009135:2,3-dihydroxybenzoic acid; D014700:Verapamil