Double-edged action of SOD mimetic in diabetic nephropathy

被引：42

作者：

Asaba, Kensuke ^{[1
]}

Tojo, Akihiro ^{[1
]}

Onozato, Maristela Lika ^{[1
]}

Goto, Atsuo ^{[1
]}

Fujita, Toshiro ^{[1
]}

机构：

[1] Univ Tokyo, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo 1138655, Japan

来源：

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY | 2007年 / 49卷 / 01期

关键词：

NADPH oxidase; superoxide dismutase; myeloperoxidase; hypochlorite; diabetic nephropathy; tempol;

D O I：

10.1097/FJC.0b013e31802b6530

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Oxidative stress plays an important role in the pathogenesis of diabetic complications, and we investigated the effect of superoxide dismutase (SOD) mimetic, tempol, in diabetic nephropathy. Streptozotocin-induced diabetic rats were treated with tempol from 2 weeks until 8 weeks. The expression of NADPH oxidase, catalase, and myeloperoxidase (MPO), superoxide dismutase activity, and production of peroxide and hypochlorite were evaluated. Tempol treatment prevented the increase in NADPH oxidase and peroxide production in the glomeruli of diabetic rat. Catalase was decreased without change in SOD activity, and MPO was enhanced in the kidney of diabetic rats. Tempol treatment stimulated SOD activity and increased the conversion Of Superoxide to hydrogen peroxide, and hydrogen peroxide on its hand was converted to hypochlorite by the increased MPO. The reduction of peroxide by tempol was followed by the decrease in TGF-beta and mesangial matrix expansion. However, tempol did not reduce hypochlorite or urinary protein excretion. In conclusion, tempol inhibited glomerular matrix expansion via suppression of peroxide production and TGF-beta, but it failed to reduce proteinuria, probably due to the increased hypochlorite production in diabetic nephropathy.

引用

页码：13 / 19

页数：7

共 37 条

[1] Effects of NADPH oxidase inhibitor in diabetic nephropathy [J].

Asaba, K ;

Tojo, A ;

Onozato, ML ;

Goto, A ;

Quinn, MT ;

Fujita, T ;

Wilcox, CS .

KIDNEY INTERNATIONAL, 2005, 67 (05) :1890-1898

[2] The pathobiology of diabetic complications - A unifying mechanism [J].

Brownlee, M .

DIABETES, 2005, 54 (06) :1615-1625

[3] Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney [J].

Chabrashvili, T ;

Tojo, A ;

Onozato, ML ;

Kitiyakara, C ;

Quinn, MT ;

Fujita, T ;

Welch, WJ ;

Wilcox, CS .

HYPERTENSION, 2002, 39 (02) :269-274

[4] Regulation and termination of NADPH oxidase activity [J].

DeCoursey, TE ;

Ligeti, E .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2005, 62 (19-20) :2173-2193

[5] The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells [J].

Djordjevic, T ;

Pogrebniak, A ;

BelAiba, RS ;

Bonello, S ;

Wotzlaw, C ;

Acker, H ;

Hess, J ;

Görlach, A .

FREE RADICAL BIOLOGY AND MEDICINE, 2005, 38 (05) :616-630

[6]

DODD OJ, 2000, AM J PHYSIOL-HEART C, V279, pH303

[7] Immunohistochemical detection of hypochlorite-modified proteins in glomeruli of human membranous glomerulonephritis [J].

Gröne, HJ ;

Gröne, EF ;

Malle, E .

LABORATORY INVESTIGATION, 2002, 82 (01) :5-14

[8] Oxidative stress in diabetic nephropathy: basic and clinical information. [J].

Ha H. ;

Lee H.B. .

Current Diabetes Reports, 2001, 1 (3) :282-287

[9] Tempol attenuates the development of hypertensive renal injury in Dahl salt-sensitive rats [J].

Hisaki, R ;

Fujita, H ;

Saito, F ;

Kushiro, T .

AMERICAN JOURNAL OF HYPERTENSION, 2005, 18 (05) :707-713

[10] Endogenous adrenomedullin protects against vascular response to injury in mice [J].

Kawai, J ;

Ando, K ;

Tojo, A ;

Shimosawa, T ;

Takahashi, K ;

Onozato, ML ;

Yamasaki, M ;

Ogita, T ;

Nakaoka, T ;

Fujita, T .

CIRCULATION, 2004, 109 (09) :1147-1153

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