Author(s): Jelenković Ankica, Jovanović Marina, Ninković Milica, Maksimović M, Bošković B
Keywords:convulsions, nitric oxide, NMDA antagonists, pentylenetetrazole, superoxide anion, superoxide dismutase
Controversy about proconvulsant and anticonvulsant nitric oxide (NO) effects and the place of oxidative stress in convulsions, are still a matter of research. We investigated the interaction between 2-amino-5- phosphonovaleric acid (APV), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and N-nitro-L-arginine methyl ester (LNAME), a nonselective nitric oxide synthase (NOS) antagonist, in pentylenetetrazole (PTZ)-induced convulsions. Pentylenetetrazole was applied to adult Wistar rats intraperitoneally (ip), in a single dose of 80 mg/kg, and L-NAME (10 μg/10 μl) or APV (20 μg/10 μl) intracerebroventricularly (icv), 30 and 10 minutes before PTZ, respectively. In the same manner, another group received both antagonists. Control animals were given 0.9% saline. N-nitro-L-arginine methyl ester exerted a weak anticonvulsant effect, preventing generalized clonic (GCC) and clonic-tonic convulsions (CTC) in 17% of cases.With APV protection against GCC and CTC was 100%, forelimb dystonia (FLD) was decreased in 33% of cases, and time to onset of all convulsive patterns was prolonged (p<0.05 to 0.01). All effects of APV, except in CTC, were reversed by L-NAME applied prior to APV. In APV-PTZ treated animals, superoxide anion content was increased in the forebrain cortex, striatum and hippocampus, without an overwhelmed antioxidative superoxide dismutase (SOD) defence system in the other treatments. When the APV-PTZ group was treated with L-NAME, both SOD activity and superoxide anion content were additionally decreased, indicating that the NOS-NO system was involved in the metabolism of superoxide anions. It is suggested that clinical and biochemical effects of NO strongly depend upon the pretreatment and might lead to a wrong impression of NO contradictory activity.
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