Double-edged action of SOD mimetic in diabetic nephropathy.
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.
Asaba
Kensuke
K
Division of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan.
Tojo
Akihiro
A
Onozato
Maristela Lika
ML
Goto
Atsuo
A
Fujita
Toshiro
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D032701:Biomimetics; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000502:physiology*
D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D013482:Superoxide Dismutase; C001803:tempol