Antioxidant SOD mimetic prevents NADPH oxidase-induced oxidative stress and renal damage in the early stage of experimental diabetes and hypertension.
OBJECTIVE
The presence of hypertension increases renal oxidative stress by increasing NADPH oxidase-dependent superoxide production and by decreasing antioxidant defense in the early stage of experimental diabetes mellitus (DM). In the present study, we investigated whether the administration of an antioxidant mimetic of the superoxide dismutase (SOD) (tempol) corrects the oxidative imbalance and oxidative stress-induced renal injury in the presence of DM and hypertension.


METHODS
DM was induced in spontaneously hypertensive rats (SHR) by streptozotocin at 4 weeks of age. The diabetic rats either did or did not receive tempol for 20 days. Oxidative-stress parameters and indices of renal injury were evaluated.


RESULTS
Tempol reestablished the imbalance in redox status induced by DM. It elevated the expression of renal antioxidant extracellular SOD, p < 0.0001; decreased (p = 0.049) the production of renal NADPH-dependent superoxide production, and diminished (p = 0.016) a marker of oxidative stress-induced DNA damage, 8-hydroxy-2'-deoxyguanosine. Reduction of oxidative stress markers was associated with reduction in renal damage parameters associated with DN. DM-induced albuminuria and elevation in renal expression of collagen IV were reduced to the level observed in control rats.


CONCLUSIONS
We conclude that an imbalance in renal redox status is associated with markers of renal injury in the early stage of DM and hypertension. Antioxidant treatment reestablished the redox status and prevented oxidative stress-induced renal damage.
Renal Pathophysiology Laboratory, Division of Nephrology, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.
Elisa B M I
EB
Peixoto
Bruno S
BS
Pessoa
Subrata K
SK
Biswas
Jose B
JB
Lopes de Faria
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D024141:Collagen Type IV / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018716:Molecular Mimicry; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D024141:Collagen Type IV; D003497:Cyclic N-Oxides; D013113:Spin Labels; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D003849:Deoxyguanosine; C001803:tempol