Reduction of circulating superoxide dismutase activity in type 2 diabetic patients with microalbuminuria and its modulation by telmisartan therapy

被引：25

作者：

Fujita, Hiroki ^{[1
]}

Sakamoto, Takuya ^{[2
]}

Komatsu, Koga ^{[2
]}

Fujishima, Hiromi ^{[1
]}

Morii, Tsukasa ^{[1
]}

Narita, Takuma ^{[1
]}

Takahashi, Takamune ^{[3
]}

Yamada, Yuichiro ^{[1
]}

机构：

[1] Akita Univ, Grad Sch Med, Div Endocrinol Metab & Geriatr Med, Akita 0108543, Japan

[2] Honjo Daiichi Hosp, Div Gastroenterol, Akita, Japan

[3] Vanderbilt Univ, Med Ctr, Div Nephrol, Nashville, TN USA

来源：

HYPERTENSION RESEARCH | 2011年 / 34卷 / 12期

关键词：

angiotensin II type 1 receptor blocker; diabetic nephropathy; oxidative stress; superoxide dismutase; telmisartan; NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; RECEPTOR BLOCKERS; HYPERTENSIVE PATIENTS; OVERT NEPHROPATHY; NAD(P)H OXIDASE; ACTIVATION; MICE; NITROTYROSINE; EXPRESSION;

D O I：

10.1038/hr.2011.127

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Growing evidence indicates that oxidative stress induced by excessive superoxide has a central role in the pathogenesis of diabetic nephropathy (DN). Telmisartan, one of the currently available angiotensin II type 1 receptor blockers (ARBs), has been shown to exert a more powerful proteinuria (albuminuria) reduction in patients with DN, but whether the prominent renoprotective effect of telmisartan is mediated through enhancing antioxidant defense capacity and reducing oxidative stress has not been fully elucidated. The present study first revealed that the serum activity of superoxide dismutase (SOD) responsible for superoxide removal is reduced in the DN stage of microalbuminuria, but not in normoalbuminuria in type 2 diabetic patients. We next examined the alteration of SOD and oxidative stress following an 8-week treatment with telmisartan (40 mg per day) in 12 type 2 diabetic patients with microalbuminuria. Interestingly, the telmisartan treatment not only reduced the circulating levels of two oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine (NT), but also enhanced serum SOD activity. Notably, a significant correlation was observed between the increase in serum SOD activity and the reduction in albuminuria. We further compared the anti-oxidative effect of telmisartan with that of losartan, another member of the ARB class, by implementing an 8-week interval crossover treatment with these ARBs in another 12 microalbuminuric type 2 diabetic patients. The patients showed higher serum SOD activity, and lower circulating levels of 8-OHdG and NT, during treatment with telmisartan than with losartan. These results suggest that telmisartan has a more potent antioxidative effect through its ability to enhance SOD activity in type 2 diabetic patients with microalbuminuria. Hypertension Research (2011) 34, 1302-1308; doi:10.1038/hr.2011.127; published online 4 August 2011

引用

页码：1302 / 1308

页数：7

共 33 条

[1] Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy [J].