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- Title
Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction.
- Authors
Moriyama, Toshiki; Kawada, Noritaka; Nagatoya, Katsuyuki; Takeji, Masanobu; Horio, Masaru; Ando, Akio; Imai, Enyu; Hori, Masatsugu; Moriyama, T; Kawada, N; Nagatoya, K; Takeji, M; Horio, M; Ando, A; Imai, E; Hori, M
- Abstract
<bold>Background: </bold>Recently, we demonstrated increased oxidative stress in the interstitium of ureteral obstructed kidneys based on the increased expression of heme oxygenase-1 and immunohistochemical detection of advanced glycation end products (AGE) in the interstitium. Antioxidant therapy may have a therapeutic potential toward interstitial fibrosis of unilateral ureteral obstruction (UUO) kidneys. Fluvastatin is an HMG-CoA reductase inhibitor and has been demonstrated to have an antioxidant activity in vitro.<bold>Methods: </bold>The effects of fluvastatin on UUO kidneys from the viewpoints of antioxidant action in vivo and antifibrosis action were studied. To investigate the antioxidant action and its therapeutic efficacy of fluvastatin in UUO kidneys, AGE accumulation and fibrosis in the obstructed kidneys was compared among vehicle-, pravastatin-, or fluvastatin-treated (10 or 40 mg/kg/day) groups.<bold>Results: </bold>Tubulointerstitial fibrosis was significantly attenuated in fluvastatin-treated animals. Fluvastatin significantly suppressed the degree of immunostaining of AGE in UUO kidneys.<bold>Conclusions: </bold>These results provide evidence for the antioxidant action of fluvastatin in vivo. The decreased interstitial fibrosis along with a decreased oxidative stress marker in the interstitial lesion strongly suggests the existence of a causal relationship between them. Fluvastatin may have therapeutic value in slowing or preventing interstitial fibrosis in progressive renal disease.
- Subjects
URETERIC obstruction; KIDNEYS; MICE; SCIENTIFIC experimentation; RNA analysis; ORGANIC compound analysis; ANIMALS; ANTILIPEMIC agents; BIOLOGICAL models; CHOLESTEROL; GENE expression; MEMBRANE proteins; MUSCLE proteins; INTERSTITIAL nephritis; OXIDOREDUCTASES; TRIGLYCERIDES; UNSATURATED fatty acids; PRAVASTATIN; OXIDATIVE stress; FIBROSIS; INDOLE compounds; PHARMACODYNAMICS
- Publication
Kidney International, 2001, Vol 59, Issue 6, p2095
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1046/j.1523-1755.2001.00724.x