Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction

Background. Recently, we demonstrated increased oxidative stress in the int erstitium of ureteral obstructed kidneys based on the increased expression of heme oxygenase-l and immunohistochemical detection of advanced glycation end products (AGE) in the interstitium. Antioxidant therapy may have a the rapeutic potential toward interstitial fibrosis of unilateral ureteral obst ruction (UUO) kidneys. Fluvastatin is an HMG-CoA reductase inhibitor and ha s been demonstrated to have an antioxidant activity in vitro. Methods. The effects of fluvastatin on UUO kidneys from the viewpoints of a ntioxidant action in vivo and antifibrosis action were studied. To investig ate the antioxidant action and its therapeutic efficacy of fluvastatin in U UO kidneys, AGE accumulation and fibrosis in the obstructed kidneys was com pared among vehicle-, pravastatin-, or fluvastatin-treated (10 or 40 mg/kg/ day) groups. Results. Tubulointerstitial fibrosis was significantly attenuated in fluvas tatin-treated animals. Fluvastatin significantly suppressed the degree of i mmunostaining of AGE in UUO kidneys. Conclusions. These results provide evidence fur the antioxidant action of f luvastatin in vivo. The decreased interstitial fibrosis along with a decrea sed oxidative stress marker in the interstitial lesion strongly suggests th e existence of a causal relationship between them. Fluvastatin may have the rapeutic value in slowing or preventing interstitial fibrosis in progressiv e renal disease.