Study of urinary 8-hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in diabetic nephropathy patients

Xu, G.W.; Yao, Qinghong; Weng, Qianfeng; Su, B.L.; Zhang, X.; Xiong, Jianhui

doi:10.1016/j.jpba.2004.04.016

Cited by 109 publications

(69 citation statements)

References 27 publications

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“…Observations highlight the relevance of mitochondrial oxidative stress in diabetic vascular complications. [22][23][24][25] Our data from ZSF 1 rats clearly demonstrated increased mitochondrial oxidative stress in the kidney as reflected by increased urinary 8-OHdG excretion and by the increased renal presence of 8-OHdG by immunohistochemistry. It is likely that atherosclerosis and hyperglycemia may cause elevation of 8-OHdG; however, the magnitude of changes BASIC RESEARCH www.jasn.org (almost eight-fold rise) seen in our study cannot be accounted for by either of those conditions, implicating renal disease as an important contributor to oxidative stress and consequent elevation of 8-OHdG.…”

Section: Discussionmentioning

confidence: 49%

“…Recent studies showed that urinary 8-OHdG not only is a measure of oxidative damage to DNA but also correlates with and is a marker of total body oxidative stress. 25 Additional studies have shown that urinary 8-OHdG correlated with the severity of DN and retinopathy 27 and also with future development of DN. 28 Others 29 have shown that in streptozotocin-induced diabetic rats, measurement of levels of 8-OHdG from mitochondrial DNA was higher in both renal cortices and papillae and so were the urinary 8-OHdG levels.…”

Section: Discussionmentioning

confidence: 99%

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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

184

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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Section: Discussionmentioning

confidence: 49%

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

184

144

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“…10 For this reason, 8-hydroxy-2¢-deoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative DNA damage in vivo, demonstrating significantly increased urinary excretion levels with severe tubulointerstitial damage. 11,12 In addition, aldosterone induces oxidative stress in vascular cells through NADPH oxidase activation, which has a central role in endothelial dysfunction and atherosclerotic vascular disease. 13 Recently, some calcium channel blockers (CCBs) have been demonstrated to exhibit an organ protection effect that is independent of their antihypertensive action.…”

Section: Introductionmentioning

confidence: 99%

Additive antioxidative effects of azelnidipine on angiotensin receptor blocker olmesartan treatment for type 2 diabetic patients with albuminuria

et al. 2011

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The present study aimed to determine whether either of two calcium channel blockers affected urinary albumin excretion or urinary levels of 8-hydroxy-2¢-deoxyguanosine (8-OHdG) and liver-type fatty acid-binding protein (L-FABP) in hypertensive diabetic patients with chronic kidney disease (CKD) who were already being treated with maximum doses of the angiotensin II receptor blocker olmesartan. We conducted an open-label, randomized, parallel-controlled study on type 2 diabetic patients with stable glycemic control who were receiving fixed doses of antidiabetic agents. The patients received either 8 mg per day azelnidipine, which was increased up to 16 mg per day (azelnidipine group; n¼34), or 2.5 mg per day amlodipine, which was increased up to 5 mg per day (amlodipine group; n¼33), over a 24-week period. Mean systolic and diastolic blood pressure decreased significantly in both groups, but there was no significant difference between the two groups at the end of the study. Serum creatinine levels and estimated glomerular filtration rate did not differ significantly between the two groups, whereas the urinary albumin/creatinine ratio and 8-OHdG and L-FABP levels decreased significantly in the azelnidipine group compared with the amlodipine group. Plasma aldosterone level was significantly decreased in the azelnidipine group, and its changes correlated significantly with those of urinary 8-OHdG and L-FABP. Our results suggest that the addition of azelnidipine to the maximal recommended dose of olmesartan was more effective in reducing albuminuria and oxidant stress in hypertensive diabetic patients with CKD than the addition of amlodipine. Hypertension Research (2011) 34, 935-941; doi:10.1038/hr.2011.67; published online 9 June 2011 Keywords: aldosterone; calcium channel blocker; chronic kidney disease; diabetic nephropathy; oxidant stress INTRODUCTIONThe importance of strict blood pressure (BP) control in patients with chronic kidney disease (CKD) was emphasized by the Japanese Society of Hypertension recommendations of a target BP of o130/ 80 mm Hg for hypertensive patients with CKD. This target is further reduced to o125/75 mm Hg for diabetic nephropathy patients whose urinary protein excretion is 41 g per day. 1 Reduction in proteinuria using suitable therapeutic interventions, similar to renin-angiotensin system (RAS) blockade an antihypertensive treatment regimen, is associated with a slower decline in renal function compared with other treatment groups with similar BPs. 2,3 RAS blockade with angiotensin-converting enzyme inhibitors or angiotensin II type-1 receptor blockers (ARBs) is currently considered the most effective pharmacological approach for renoprotection. These agents reduce proteinuria more effectively than other antihypertensive drugs, and therefore, RAS inhibitors should be titrated to maximal recommended doses. 1,4 However, it is difficult to control BP with mono-

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“…In particular, it has been suggested that DNA oxidation favors early expression of a renal phenotype of progressive glomerular cell senescence and proteinuria associated with accelerated endothelial and vascular cell senescence and atherogenesis (10). This hypothesis is supported by evidences that a biomarker of oxidative DNA damage, the 8-hydroxydeoxyguanosine, is more excreted in albuminuric than in normoalbuminuric diabetic patients (14) and that plasma 8-hydroxydeoxyguanosine is related to enhanced diabetic nephropathy (15). The findings of Tentolouris et al also lead the authors to hypothesize that arterial stiffness, found in patients with microalbuminuria, may be due to the more pronounced "aging" of these patients.…”

mentioning

confidence: 97%

Pathogenetic Loop Between Diabetes and Cell Senescence

Testa¹,

Ceriello

2007

Diabetes Care

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Study of urinary 8-hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in diabetic nephropathy patients

Cited by 109 publications

References 27 publications

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

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

Additive antioxidative effects of azelnidipine on angiotensin receptor blocker olmesartan treatment for type 2 diabetic patients with albuminuria

Pathogenetic Loop Between Diabetes and Cell Senescence

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