7-nitroindazole reduces nitrite concentration in rat brain after intrahippocampal kainate-induced seizure.
Kainic acid is an endogenous excitotoxin acting on glutamate receptors, that leads to neurotoxic damage resembling the alterations observed in some neurological disorders. Stimulation of glutamate receptors induces neuronal nitric oxide (NO) release, which in turn modulates glutamate transmission. NO may be a key mediator of excitotoxic neuronal injury in the central nervous system. We investigated the effects of 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor in vivo, on nitrite concentration after kainic acid injection (0.6 mg/ml, pH 7.2) unilaterally into the CA3 region of the rat hippocampus. The accumulation of nitrite, the stable metabolite of NO, was measured by the Griess reaction at different times (5 min, 15 min, 2 h, 48 h and 7 days) following kainate injection in the ipsilateral and contralateral hippocampus, forebrain cortex, striatum and cerebellum homogenates. 7-Nitroindazole (100 microM) can effectively inhibit NO synthesis in rat brain after kainate-induced intrahippocampal neurotoxicity and suppressed nitrite accumulation. The present results suggest that neuronal NO synthase inhibitors may be useful in the treatment of neurological diseases where excitotoxic mechanisms play a role.
Radenovic
Lidija
L
Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski Trg 16, Belgrade 11000, Serbia and Montenegro. lira@ibiss.bg.ac.yu
Vasiljevic
Ivana
I
Selakovic
Vesna
V
Jovanovic
Marina
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology*; D007608:Kainic Acid / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D009573:Nitrites / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007191:Indazoles; D009573:Nitrites; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D007608:Kainic Acid; C080122:7-nitroindazole