RESUMEN
Polyamines are aliphatic amines containing nucleophilic centers that are found in all eukaryotic cells, including brain cells. These compounds determine neuroprotection in experimental models of cerebral ischemia and neurotoxicity. In the current study we investigated the protective effects of spermine, an agonist of the polyamine binding site at the N-methyl-d-aspartate receptor, against the behavioral and neurochemical alterations induced by quinolinic acid. The unilateral intrastriatal injection of quinolinic acid (180 nmol/site into the dorsal striatum) induced stereotypical motor asymmetries, assessed by the open field and elevated body swing tests. Spermine modulated quinolinic acid-induced rotational behavior biphasically. While the previous intrastriatal administration of spermine at the dose of 0.1 nmol/site increased, the administration of spermine at the dose of 10 nmol/site reduced quinolinic acid-induced rotational behavior. Spermine (10 nmol/site) also decreased the contralateral swing behavior induced by quinolinic acid. Furthermore, the effect of 10 nmol of spermine was counteracted by the co-administration of arcaine (10 nmol), a selective antagonist of the polyamine binding site at the N-methyl-d-aspartate receptor. In addition, spermine (10 nmol) protected against quinolinic acid-induced protein carbonylation in the rat striatum, further suggesting an antioxidant role for this polyamine. These results provide evidence that the behavioral and biochemical alterations induced by quinolinic acid are attenuated or prevented by spermine through its interaction with N-methyl-d-aspartate receptor and/or its antioxidant function.
Asunto(s)
Antioxidantes/metabolismo , Química Encefálica/fisiología , Cuerpo Estriado/metabolismo , Estrés Oxidativo/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Espermina/metabolismo , Animales , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Biguanidas/farmacología , Sitios de Unión/efectos de los fármacos , Sitios de Unión/fisiología , Unión Competitiva/efectos de los fármacos , Unión Competitiva/fisiología , Química Encefálica/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Antagonistas de Aminoácidos Excitadores/farmacología , Masculino , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Estrés Oxidativo/efectos de los fármacos , Ácidos Quinolínicos/antagonistas & inhibidores , Ácidos Quinolínicos/farmacología , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Espermina/farmacologíaRESUMEN
Polyamines, among other functions, are considered to act as a free radical scavenger and antioxidant. The quinolinic acid (QA), sodium nitroprusside (SNP) and iron (Fe+2) stimulate production of free radicals and lipid peroxidation. In the present study, we investigated the free radical and/or aldehyde scavenger effects of polyamines spermine and spermidine on thiobarbituric acid reactive species (TBARS) production induced by QA, SNP, Fe+2/EDTA system and free Fe2+ in rat brain. Spermine and spermidine inhibited QA-induced TBARS production; however spermine was a better antioxidant than spermidine. Spermine also inhibited SNP-, Fe+2/EDTA- and free Fe2+-induced TBARS production, but had a modest effect. Spermidine, in turn, also discretely inhibited SNP-, Fe+2/EDTA- and free Fe2+-induced TBARS production. In the presence of MK-801, QA-induced TBARS production was considerably more inhibited by polyamines. In addition, arcaine does not affect the reducer effect of polyamines. The present findings suggest that the observed effects of polyamines are not related to the activation of NMDA receptor but with their antioxidant and free radical scavenger properties.
