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Journal of Medical Biochemistry
2015, vol. 34, br. 4, str. 422-430
jezik rada: engleski
vrsta rada: izvorni naučni članak
doi:10.1515/jomb-2015-0001
Farmakogenetika može imati uticaja na dnevnu dozu takrolimusa, ali ne i na markere tubularnog oštećenja u dugoročnom periodu nakon transplantacije bubrega
aUniversity of Niš, Faculty of Medicine, Department of Pharmacy
bUniversity of Niš, Faculty of Medicine, Institute of Biochemistry + Clinical Centre Niš, Clinic of Nephrology
cUniversity of Niš, Faculty of Medicine, Department of Pharmacy + Clinical Centre Niš, Clinic of Nephrology
dUniverzitet u Nišu, Medicinski fakultet

e-adresa: snikola84@gmail.com

Projekat

Preventivni, terapijski i etički pristup prekliničkim i kliničkim istraživanjima gena i modulatora redoks ćelijske signalizacije u imunskom, inflamatornom i proliferativnom odgovoru ćelije (MPNTR - 41018)

Sažetak

Uvod: Primarni cilj ovog rada bio je procena uticaja citohrom P450 (CYP) 3A5 (6986A>G ) i ABCB1 (3435C>T) polimorfizama na dozni režim i izloženost takrolimusu (TAC). Sekundarni cilj bio je procena uticaja doznog režima TAC i ispitivanih polimorfizama na renalni oksidativni stres, kao i na urinarnu aktivnost tubularnih ektoenzima u dugoročnom periodu nakon transplantacije. Takođe, mi smo imal i za cilj da odredimo povezanost između renalnog oksidativnog stresa i markera tubularnog oštećenja kod pacijenata sa transplantiranim bubregom. Metode: Istraživanje je uključivalo 72 pacijenata, koji su bili na TAC imunosupresivnom režimu. Alel-specifični PCR metod je korišćen u cilju određivanja polimorfizama. Mi smo određivali nivo tiobarbituratna kiselina reaktivnih supstanci (TBARS) i reaktivnih karbonilnih grupa (RCD) u urinu u cilju procene oksidativnog stresa i aktivnosti ektoenzima (N-acetil-b-D-glukozaminidaza, aminopeptidaza N i dipeptidil peptidaza IV) u urinu, kao markere oštećenja tubula. Rezultati: Nosioci CYP 3A5*1 alela imali su statistički veće dnevne doze TAC u poređenju sa nosiocima CYP *3/*3 genotipa, kao i nosioci C alela ABCB1 genskog polimorfizma u poređenju sa nosiocima TT genotipa. Takođe, nije bilo razlika u nivoima TBARS, RCD i aktivnostima ektoenzima između različitih genotipova pacijenata. Naši rezultati pokazali su značajne korelacije između urinarnog TBARS i RCD i aktivnosti ektoenzima. Zaključak: Nasi rezultati ukazuju na to da CYP 3A5 i ABCB1 3435 polimorfizam mogu uticati na dnevnu dozu TAC, ali ne i na tubularnu toksičnost izazvanu lekom. Pored toga, oštećenje tubula može biti udruženo sa povećanim renalnim oksidativnim stresom.

Ključne reči

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