대한신장학회

Skip Navigation: Skip to contents

KOR
ENG
전체메뉴보기

간행물 검색

현재 페이지 경로

HOME
간행물
간행물 검색

논문분류	춘계학술대회 초록집
제목	The Protective Effect of Febuxostat on Chronic Tacrolimus-induced Nephrotoxicity in Rats
저자	Hyun Seon Kim*
출판정보	2016; 2016(1):
키워드	Febuxostat, Hyperuricemia, Nephropathy, Oxidative stress, Tacrolimus
초록	Background: Background: Calcineurin inhibitors (CNIs) are a well-known risk factor for hyperuricemia in kidney transplant (KT) recipients. We evaluated the effect of febuxostat (Fx), a new uric acid lowering drug, on hyperuricemia and renal injury in experimental model of chronic tacrolimus (Tac)-induced nephropathy. Methods: Method: treating Tac (1.5mg/kg/day) on a low salt diet (0.05%) with oxonic acid (OA, 2%, 0.2g/kg/day) for 28 days in rats. Two doses of Fx (5 and 10mg/kg) were concomitantly administered with Tac or vehicle (Vh).We evaluated the effect of Fx on hyperuricemia by serum uric acid levels, fractional excretion of uric acid (FEUA), and urate transporters in Tac-induced nephropathy. The effect of Fx on Tac-induced renal injury was evaluated by renal function and pathology. As a protective mechanism, we evaluated oxidative stress in terms of xanthine oxidase (XO) activity and the marker of oxidative stress [8-hydroxy-2’-deoxyguanosine (8-OHdG) and 4-hydroxy-2-hexenal (4-HHE)]. Results: Results: The Tac group showed higher serum uric acid levels and lower FEUA than the Vh group, but Fx treatment significantly decreased serum uric acid level in a dose-dependent manner with increase of FEUA at high dose (10 mg/kg). Tac treatment increased urate-anion exchanger 1 and decreased organic anion transporter type 1 expressions in renal tubular cells, but Fx treatment reversed those transporters. Impaired renal function and histological injury (interstitial fibrosis, inflammation and arteriolopathy) in the Tac group were markedly improved with Fx treatment. Increased apoptotic cell death and activated proapoptotic caspase 3 by Tac was remarkably decreased with Fx treatment. Tac treatment increased activity of XO in kidney tissue and serum, and level of 8-OHdG in urine and 8-OHdG and 4HHE of kidney tissue, but combined treatment with Fx decreased those parameters. Conclusion: Conclusions: Fx is effective in control hyperuricemia and in preventing Tac-induced renal injury via the reduction of oxidative stress.
원문(PDF)	PDF 원문보기

목록

위로가기