Attenuation of Renal Injury in <i>db</i>/<i>db</i> Mice Overexpressing Superoxide Dismutase

DeRubertis, Frederick R.; Craven, Patricia A.; Melhem, Mona F.; Salah, Eman

doi:10.2337/diabetes.53.3.762

Cited by 128 publications

(114 citation statements)

References 51 publications

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“…This study is the first to show the close relationship between antioxidant capacity and microalbuminuria in type 2 diabetic patients. A relationship had previously only been demonstrated in mice with experimental diabetes, where transgenic overexpression of superoxide dismutase attenuated renal injury, including increased AER [40].…”

Section: Discussionmentioning

confidence: 95%

Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients

et al. 2009

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Aims/hypothesis This study examined the relationship, if any, between glucose-induced oxidative stress, antioxidant status and microalbuminuria in patients with type 2 diabetes. Methods The study involved 99 consecutive type 2 diabetic patients (57 men, 42 women). Patients with persistent microalbuminuria were identified and the following variables evaluated: fasting plasma glucose, HbA 1c , malonyldialdehyde (MDA), pentosidine, AGE, the total radical-trapping antioxidant parameter (TRAP), vitamin E, creatinine, estimated GFR and lipid profile. Results Patients were divided into two groups, i.e. 37 individuals without microalbuminuria (AER <20 μg/min) and 62 with microalbuminuria (AER ≥20 μg/min). The following variables were significantly higher in patients with microalbuminuria than in those without microalbuminuria (mean ± SD): fasting plasma glucose 9.41±2.88 vs 8.19±1.93 mmol/l, p<0.05; HbA 1c 7.97±1.51 vs 7.39± 1.03%, p<0.05; MDA 1.18±0.35 vs 1.02±0.29 µmol/l, p< 0.05; pentosidine 98.5±24.6 vs 82.9±20.9 pmol/ml, p< 0.005; and AGE 13.2±4.8 vs 10.6±3.8 µg/mg protein, p< 0.01. However, vitamin E and TRAP did not differ between the two groups. Serum creatinine values and estimated GFR were similar in the two groups. Only in patients with microalbuminuria were significant linear correlations seen between AER and both oxidation (HbA 1c r=0.33, p<0.01; MDA r=0.59, p<0.001; pentosidine r=0.48, p<0.001; and AGE r=0.44, p<0.001) and antioxidation variables (vitamin E r=−0.55, p<0.001; TRAP r=−0.49, p<0.001). Considering all variables together, multiple regression revealed a correlation between microalbuminuria and vitamin E, TRAP, HbA 1c and MDA, but not pentosidine or AGE. Conclusions/interpretation Our data suggest that microalbuminuria in type 2 diabetic patients might be promoted by an insufficient counter-regulation of the antioxidant system in the event of increased glyco-oxidation/glycation.

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Section: Discussionmentioning

confidence: 95%

Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients

et al. 2009

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“…155 Consumption of dark chocolate is associated with blood pressure reduction associated with a reduction in oxidative stress and increase in nitric oxide bioavailability, 156 both abnormalities that have been involved in the pathogenesis of diabetic nephropathy and retinopathy. 67,[85][86][87][88][93][94][95][97][98][99]156 Finally, in experimental diabetes, the use of green tea was associated with an improvement in diabetic nephropathy and retinopathy and associated with a reduction in oxidative stress. 91, 157 The usefulness of these dietary approaches in diabetic patients with hypertension and nephropathy or retinopathy that are on standard treatment deserves to be tested in larger clinical trials.…”

Section: Discussionmentioning

confidence: 97%

“…87 However, long-term diabetes alone is sufficient to increase renal oxidative stress, as shown in many different studies. 67,88,89 Interestingly, it has been shown that tempol, an antioxidant mimetic of superoxide dismutase, is renal protective when administered to diabetic SHRs. In STZ-induced DM SHRs, the use of tempol for 20 days normalized renal cortical extracellular superoxide dismutase expression and decreased superoxide generation and oxidative stressinduced DNA damage.…”

Section: Inflammation and Oxidative Stress As The Underlying Mechanismentioning

confidence: 99%

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

2011

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Diabetes and hypertension frequently coexist and constitute the most notorious combination for the pathogenesis of diabetic nephropathy and retinopathy. Large clinical trials have clearly demonstrated that tight control of glycemia and/or blood pressure significantly reduces the incidence and progression of diabetic retinopathy (DR) and nephropathy. However, the mechanism by which hypertension interacts with diabetes to induce and/or exacerbate nephropathy and retinopathy is very unclear. Substantial evidence implicates the involvement of chronic inflammation and oxidative stress in the pathogenesis of DR and nephropathy. In addition, hypertension causes oxidative stress and inflammation in the kidney and retina. In the present review, we summarized data obtained from our research along with those from other groups to better understand the role of hypertension in the pathogenesis of diabetic nephropathy and retinopathy. It is suggested that oxidative stress and inflammation may be common denominators of kidney and retinal damage in the concomitant presence of diabetes and hypertension.

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“…When such damaged DNA is repaired, 8-OHdG is produced and excreted unchanged in the urine. 15 Previous studies 16 in experimental diabetes demonstrated decreased renal NO levels as a consequence of increased oxidative stress, primarily as a result of enhanced expression of superoxide dismutase and catalase. In those studies, NOS expression was not studied.…”

Section: Discussionmentioning

confidence: 99%

Diabetic Nephropathy Is Associated with Oxidative Stress and Decreased Renal Nitric Oxide Production

Prabhakar¹,

Starnes²,

Shi³

et al. 2007

Journal of the American Society of Nephrology

183

144

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The pathogenesis of diabetic nephropathy remains far from clear, partly due to the lack of a suitable animal model that mimics human renal disease in type 2 diabetes. In this study, the natural history of renal manifestations in ZSF 1 rats, a recently developed rodent model of type 2 diabetes, is described. Male ZSF 1 rats developed obesity and hyperglycemia by 20 weeks of age on a highcarbohydrate diet. They also developed systolic and diastolic hypertension, hypercholesterolemia, profound hypertriglyceridemia, proteinuria, and renal failure. Renal histology demonstrated changes consistent with early diabetic nephropathy, including arteriolar thickening, tubular dilation and atrophy, glomerular basement membrane thickening, and mesangial expansion. Furthermore, renal nitric oxide production was decreased, and homogenates from renal cortices demonstrated reduced expression of renal endothelial and inducible nitric oxide synthases. These changes were associated with increased urinary levels and renal expression of 8-hydroxydeoxyguanosine, an indicator of mitochondrial oxidative stress, as well as with increased renal peroxynitrite formation. Administration of either insulin or the antioxidant alpha-lipoic acid decreased proteinuria and oxidative stress, but only the former slowed progression of renal failure. We conclude that ZSF 1 rats represent the best available rat model to study nephropathy from type 2 diabetes and that the renal lesions are associated with increased oxidative stress and decreased renal nitric oxide availability. 18: 294518: -295218: , 200718: . doi: 10.1681 Despite several recent advances, the pathogenesis of diabetic nephropathy (DN) remains far from clear. 1 The lack of suitable diabetic animal models that develop nephropathy akin to human disease is a major barrier for progress in this field. Notwithstanding the contribution to mechanistic pathways, the in vitro models to study DN have compounded the problem, necessitating more dependable in vivo animal models. Furthermore, the growing epidemic of metabolic syndrome warrants need for animal models that develop hyperlipidemia and obesity in addition to maturity-onset diabetes to mimic complications of human diabetes and metabolic syndrome. We report here a genetically engineered rat that developed features of DN as well as full-blown metabolic syndrome. Furthermore, decreased renal nitric oxide (NO) production was noted in these rats, consistent with our previous observations in mesangial cell cultures in vitro that were exposed to high ambient glucose concentrations. These changes were associated with increased oxidative stress, which partly accounted for decreased NO levels. J Am Soc Nephrol

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Attenuation of Renal Injury in db/db Mice Overexpressing Superoxide Dismutase

Cited by 128 publications

References 51 publications

Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients

Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

Diabetic Nephropathy Is Associated with Oxidative Stress and Decreased Renal Nitric Oxide Production

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