Oxidative damage to DNA and lipids: correlation with protein glycation in patients with type 1 diabetes

Goodarzi, Mohammad Taghi; Navidi, Ali A.; Rezaei, Maryam; Babahmadi-Rezaei, Hossein

doi:10.1002/jcla.20328

Cited by 80 publications

(49 citation statements)

References 32 publications

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“…Diabetes and elevated levels of arginase activity and expression are associated with increased levels of ROS (15). Our study showed that whole body levels of ROS are elevated in diabetic WT mice, as indicated by measurements of plasma lipid hydroperoxide levels.…”

Section: Rossupporting

confidence: 58%

Diabetes-induced vascular dysfunction involves arginase I

Romero¹,

Iddings²,

Platt³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Arginase can cause vascular dysfunction by competing with nitric oxide synthase for L-arginine and by increasing cell proliferation and collagen formation, which promote vascular fibrosis/stiffening. We have shown that increased arginase expression/activity contribute to vascular endothelial cell (EC) dysfunction. Here, we examined the roles of the two arginase isoforms, arginase I and II (AI and AII, respectively), in this process. Experiments were performed using streptozotocin-induced diabetic mice: wild-type (WT) mice and knockout mice lacking the AII isoform alone (AI ϩ/ϩ AII Ϫ/Ϫ ) or in combination with partial deletion of AI (AI ϩ/Ϫ AII Ϫ/Ϫ ). EC-dependent vasorelaxation of aortic rings and arterial fibrosis and stiffness were assessed in relation to arginase activity and expression. Diabetes reduced mean ECdependent vasorelaxation markedly in diabetic WT and AI ϩ/ϩ AII mice. In diabetic WT and AI ϩ/ϩ AII Ϫ/Ϫ mice, aortic arginase activity and AI expression were significantly increased compared with control mice, but neither parameter was altered in AI ϩ/Ϫ AII Ϫ/Ϫ mice. In summary, AI ϩ/Ϫ AII Ϫ/Ϫ mice exhibit better EC-dependent vasodilation and less vascular stiffness and coronary fibrosis compared with diabetic WT and AI ϩ/ϩ AII Ϫ/Ϫ mice. These data indicate a major involvement of AI in diabetes-induced vascular dysfunction. fibrosis; oxidative stress; vascular stiffness IN VASCULAR ENDOTHELIAL CELLS (ECs), nitric oxide (NO) synthase (NOS) uses L-arginine to produce NO, which maintains blood flow and reduces inflammation (21,22). Reduced availability of L-arginine to NOS and the resultant reduction of NO production have been implicated in the vascular dysfunction associated with diabetes and other cardiovascular disease states. Acute L-arginine supplementation can prevent or reverse EC dysfunction and restore EC-dependent vasodilation in diabetes (1, 31). Reduced availability of L-arginine for NOS can occur via increased activity or expression of arginase, an enzyme that competes with NOS for L-arginine, producing ornithine and urea.Two isoforms of arginase exist in mammals, arginase I and II (AI and AII, respectively) (8, 23). AI, which is located in the cytoplasm, is expressed most abundantly in liver, whereas AII is a mitochondrial enzyme expressed primarily in the kidney. Both AI and AII have been found in EC populations (11, 34). During diabetes, impaired vascular function is closely associated with oxidative stress and inflammation (12, 28), both of which have been associated with elevated arginase activity and expression (4, 18).Enhanced arginase activity appears to be involved in conditions characterized by vascular endothelial dysfunction (VED), such as diabetes, pulmonary hypertension, ischemia-reperfusion, and aging (5,19,29,33, 42). Additionally, high chronic L-arginine intake can induce arginase expression/activity, thereby inducing vascular dysfunction (20,21,30,35). Competition between arginase and NOS for their common substrate, arginine, suggests a cause-and-effect relationship in which...

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Section: Rossupporting

confidence: 58%

Diabetes-induced vascular dysfunction involves arginase I

Romero¹,

Iddings²,

Platt³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…18,19 Increased oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications including nephropathy. 20 Diabetic hyperglycemia is associated with increased production of reactive oxygen species. 20 Reactive oxygen species damage to DNA necessitates the induction of various DNA repair processes, which can result in the urinary excretion of products such as 8-OHdG.…”

Section: Discussionmentioning

confidence: 99%

“…20 Diabetic hyperglycemia is associated with increased production of reactive oxygen species. 20 Reactive oxygen species damage to DNA necessitates the induction of various DNA repair processes, which can result in the urinary excretion of products such as 8-OHdG. 21 Urinary 8-OHdG is therefore a sensitive biomarker of oxidative DNA damage, and is also significantly correlated with the severity of tubulointerstitial lesions.…”

Section: Discussionmentioning

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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“…A previous study conducted in Type 2 diabetes mellitus (n=60) and controls (n=60) indicated that oxidative stress ratio and DNA damage was found to be increased in patients than in controls [40]. A study conducted among Bangladeshi population has also reported that DNA damage is closely [42]. A study conducted in Mexican population indicated a lack of association between diabetes and DNA damage [43].…”

Section: Association Between Tas Dna Damage and Type 2 Diabetes Melmentioning

confidence: 98%

Assessment of Dna Strand Breaks and Total Antioxidant Status in Type 2 Diabetic Patients With and Without Complications- A Case-Control Study

Nithya

Isabel²,

Angeline³

et al. 2017

Asian J Pharm Clin Res

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Objective: To evaluate the total antioxidant status (TAS) and the extent of DNA strand breaks (damage) as a measure of oxidative stress biomarkers in patients with Type 2 diabetes (with and without complications) and controls.Methods: Blood samples were collected from 200 patients with Type 2 diabetes mellitus (n=100, with complications and n=100, without complications) and 100 healthy individuals. Oxidative DNA damage was evaluated using alkaline single cell gel electrophoresis (comet assay). TAS was assessed by ferric reducing ability of plasma assay.Results: TAS was found to be significantly lower in patients with Type 2 diabetes (with and without complications) compared to controls (p<0.001). Similarly, patients with complications of Type 2 diabetes mellitus had significantly lower TAS when compared to patients with diabetes (p=0.007). DNA damage analysis showed that the extent of damage was high in patients with diabetes mellitus (with and without complications) compared to controls (p<0.001). Fasting glucose and glycosylated hemoglobin level (HbA 1C ) were found to be significantly higher in patients with diabetes than controls (p<0.05). Correlation analysis showed that there is no association between age, duration, sugar level, HbA 1C , TAS, and DNA damage in patients with Type 2 diabetes mellitus. Conclusion:Alterations in TAS and the extent of DNA damage were observed in patients with complications of diabetes mellitus indicate that oxidative stress is more in patients with complications when compared to patients without complications and healthy individuals. Therefore, further DNA damage and onset of complications in Type 2 diabetes mellitus could be prevented by counteracting the oxidative stress by therapeutic interventions using appropriate antioxidants.

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Oxidative damage to DNA and lipids: correlation with protein glycation in patients with type 1 diabetes

Cited by 80 publications

References 32 publications

Diabetes-induced vascular dysfunction involves arginase I

Diabetes-induced vascular dysfunction involves arginase I

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

Assessment of Dna Strand Breaks and Total Antioxidant Status in Type 2 Diabetic Patients With and Without Complications- A Case-Control Study

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