Uticaj spermina i L-name na metabolizam poliamina i azot monoksida u mozgu pacova u toku konvulzija

Abstract

In the CNS polyamines can exert opposite effects, depending on the concentration and conditions in the cell. Protective or neurotoxic polyamine effects were documented during seizures and repeated CNS excitation. Intensive research of exogenous polyamines effects during seizures induced by numerous agents did not clear up confusions about the duality of effects and the role of polyamines in seizures. In order to understand polyamine modulatory effects in seizures, the importance of NO and polyamine metabolism interdependence and the possible implication of changes of postulated NO and polyamine equillibrium in seizures, the effects of spermine alone and in combination with L-NAME (NOS inhibitor) on seizures induced by pentazol (PTZ) were investigated. To compare the obtained results, the effects of anticonvulsant midazolam on NO production during seizures were also investigated. Seizures were induced by i.p. application of pentazol (100 mg/kg b.w). Spermine and L-NAME were administered i.p. before PTZ. In the striatum and hippocampus, spermine induced increased NO production (p<0.001) related to values in the group treated by PTZ. Application of L-NAME before spermine and PTZ caused decrease of NO production in comparison with animals treated only by PTZ or spermine and PTZ. L-NAME given before spermine exerts protective effects related to seizures induced by PTZ and to the group treated by spermine, extending the time of seizure symptoms appearance, thus confirming the NO signaling system involvement in spermine effects during seizures. Highly significant PAO activity increase caused by spermine points out the intensified interconversion of spermine into putrescine, in order to maintain the intracellular putrescine concentration. The obtained results prove a strong relationship between the NO signaling system and polyamine metabolism in the brain during seizures and the importance of their changes in this kind of CNS injury.

U CNS-u poliamini mogu imati dijametralno suprotne efekte, zavisno od njihove koncentracije i uslova u ćeliji. U toku konvulzija i pri ponavljanoj ekscitaciji CNS-a dokazani su i protektivni i neurotoksični efekti poliamina. Intenzivna istraživanja efekata egzogenih poliamina u toku konvulzija izazvanih brojnim agensima in vivo nisu još uvek razjasnila nedoumice o dualitetu efekata i ulozi poliamina u konvulzijama. U cilju razjašnjenja modulatornih efekata poliamina u konvulzijama, značaja povezanosti metabolizma NO i poliamina i mogućnosti implikacije promena postulirane ravnoteže između NO i poliamina u konvulzijama, ispitivani su efekti spermina na konvulzije izazvane pentazolom (PTZ) i produkciju NO, kao i efekti spermina u kombinaciji sa L-NAME (inhibitorom NOS). Radi poređenja dobijenih rezultata, ispitivani su i efekti antikonvulziva midazolama na produkciju NO u toku konvulzija. Konvulzije su izazivane i.p. aplikacijom pentazola (100 mg/kg TM). Spermin i L-NAME su aplikovani i.p. pre PTZ-a. U strijatumu i hipokampusu spermin izaziva povećanu produkciju NO (p<0,001) u odnosu na vrednosti u grupi tretiranoj PTZom. Aplikacija L-NAME pre spermina i PTZ-a izazvala je smanjenje produkcije NO u odnosu na životinje tretirane samo PTZ-om ili sperminom i PTZ-om. Primena spermina pre pentazola produbljuje kliničke efekte pentazola. L-NAME, dat pre spermina, ispoljava protektivne efekte u odnosu na konvulzije izazvane pentazolom i grupu tretiranu sperminom, produžavajući vreme pojave simptoma konvulzija, što potvrđuje uključenost NO signalnog sistema u efekte spermina u toku konvulzivne aktivnosti. Visokosignifikantni porast aktivnosti PAO izazvan sperminom ukazuje na intenzivnu interkonverziju poliamina u putrescin u cilju održanja intracelularne koncentracije putrescina. Dobijeni rezultati dokazuju povezanost NO signalnog sistema i metabolizma poliamina i značaj njihovih promena u ovoj vrsti oštećenja CNS-a.