Terapijski potencijal agmantina u eksperimentalnom autoimunskom encefalomijelitisu
Sažetak
Uvod/Cilj. Eksperimentalni autoimunski encefalomijelitis (EAE) je model multiple skleroze (MS) u kome su ispitivani neuroprotektivni efekti agmatina (AGM), poznatog primarnog amina koji se dobija dekarboksilacijom L-arginina. Metode. Dark Aguti pacovi su podeljeni u grupe: kontrola (C), kompletni Frojdov adjuvans (CFA), EAE pacovi dekapitovani 13 dana (EAE13) i 20 dana (EAE20) nakon imunizacije, EAE životinje sa tri (EAE+AGM13) i 10 (EAE+AGM20) doza AGM i zdrave životinje sa tri/10 doza AGM (AGM). Reaktivne supstance koje reaguju sa tiobarbiturnom kiselinom (TBARS), SH grupe (SH), koncentracija ukupnog glutationa (GSH), aktivnost glutation peroksidaze (GPx), aktivnost superoksid dizmutaza (tSOD, MnSOD, CuZnSOD) i koncentracija nitrita/nitrata (NO2+NO3) su određivani u plazmi i moždanim strukturama [kompletna encefalitična masa (WEM) i produžena moždina (BS)]. Rezultati. Dobijeni rezultati su pokazali da tretman sa AGM uspešno smanjuje teški klinički deficit u EAE. Aplikacija AGM kod EAE pacova je normalizovala TBARS, SH, GSH, GPx i NO u WEM. U BS, AGM je doveo do manje izraženih efekata normalizacijom TBARS, GPx i NO, ali je bio bez efekata na SH grupe i GSH. U obe moždane strukture, tSOD je bila smanjena i normalizovana u piku i remisiji bolesti nakon tretmana sa AGM. Efekat AGM na MnSOD u EAE je bio izražen u WEM/BS samo u toku remisije bolesti i manifestovao se kao redukcija aktivnosti enzima. Zaključak. Blaža forma razvijenog EAE pokazuje izraženi terapijski efekat AGM kod MS. Aktivirani antioksidativni sistem i supresija razvoja oksidativnog/ nitrozativnog stresa mogu predstavljati uspešnu blokadu neuroinflamacije indukovanu EAE imunizacijom. Studija pokazuje sposobnost AGM da ublaži oksidativno/ nitrozativno oštećenje u piku EAE modulacijom kapaciteta antioksidativne odbrane u toku trajanja bolesti. U tom smislu, AGM se može smatrati agensom za antioksidativno lečenje i prevenciju neuroinflamacije u EAE.
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