UTICAJ HEKSAVANADATA NA AKTIVNOST Na+/K+-ATPaze
Sažetak
Uvod: Poslednjih godina postoji veliko interesovanje za primenu polioksometalata u kliničkoj medicini, pre svega kao antikancer, antibakterijskih, antivirusnih i antikoagulantnih agenasa. Polazeći od ključne uloge Na+/K+-ATPaze u normalnom funkcionisanju gotovo svih animalnih ćelija, razvoju nekih patoloških stanja i toksikološkog značaja ovog enzima cilj ovog rada je ispitivanje in vitro uticaja četiri novo sintetisana heksavanadata: [V6-CH3][Na]2, [V6-NO2][TBA]2, [V6-C3][H]2, [V6-C5d][TBA]2 na aktivnost Na+/K+-ATPaze.
Materijal i metode:U eksperimentu je praćena enzimska aktivnost Na+/K+-ATPaze cerebralnog korteksa svinje u odsustvu i prisustvu različitih koncentracija heksavanadata (u opsegu od 10-8 do 10-3 mol/L) [V6-CH3][Na]2, [V6-NO2][TBA]2, [V6-C3][H]2, [V6-C5d][TBA]2. Specifična aktivnost enzima praćena je spektrofotometrijskim merenjima na Perkin Elmer Lambda 35 UV-VIS spektrofotometru, merenjem koncentracije neorganskog fosfata oslobođenog enzimskom hidrolizom ATP-a.
Rezultati: Ispitivana jedinjenja inhibiraju aktivnost Na+/K+_ATPaze na dozno zavisan način u ispitivanom opsegu koncentracija. Dobijeni rezultati pokazuju da sva ispitivana jedinjenja inhibiraju aktivnost Na+/K+ ATPaze, ali da imaju različite inhibicione moći. Jedinjenje [V6-NO2][TBA]2 je najpotentniji inhibitor Na+/K+ ATPaze (IC50 = 1,87 × 10-5 mol/L), dok jedinjenje [V6-C5d][TBA]2 pokazuje najslabiji inhibitorni uticaj (IC50 = 1,31 × 10-4 mol/L). Dobijeni rezultati su u saglasnosti sa ranije pokazanim inhibitornim efektom polioksometalata (uključujući polioksovanadate) na aktivnost ATPaza različitog porekla.
Zaključak: Na osnovu dobijenih rezultata možemo da zaključimo da ispitivani heksavanadati na fiziološkoj pH vrednosti inhibiraju aktivnost Na+/K+ATPaze, kao i da je dobijena inhibicija dozno-zavisna. Inhibitorne moći heksavanadata testiranih u ovom radu se međusobno razlikuju, i slabije su od inhibitornog efekta (ranije ispitivanog) dekavanadata na aktivnost Na+/K+ATPaze, što je verovatno posledica razlika u naelektrisanju, veličini i obliku ovih poliokosmetalata. Imajući u vidu ulogu ovih enzima u funkcionisanju zdrave ćelije i razvoju patoloških stanja, moguće je da inhibicija ovih enzima polioksometalatima doprinosi (in vitro i in vivo potvrđenim) antitumorskim, antiviralnim i antibakterijskim osobinama polioksometalata.
Ključne reči: Na+/K+-ATPaza, polioksometalati, inhibicija, heksavanadati (V6).
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