Oxidative damage to mitochondrial DNA and its relationship to diabetic complications

Suzuki, Susumu; Hinokio, Yoshinori; Komatu, Koga; Ohtomo, Masataka; Onoda, Masatoshi; Hirai, Satoshi; Hirai, Masashi; Hirai, Atsuko; Chiba, Masaki; Kasuga, Shigeru; Akai, Hiroaki; Toyota, Takayoshi

doi:10.1016/s0168-8227(99)00046-7

Cited by 126 publications

(79 citation statements)

References 22 publications

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“…Notably, we first determined that the salivary 8-OHdG levels of periodontitis patients with deleted mtDNA were significantly higher than those of patients with non-deleted mtDNA and that there was a positive correlation between salivary 8-OHdG level and the occurrence of the 5-kbp mtDNA deletion in diseased gingival tissues. Similar correlations were previously reported by Kakimoto et al (Kakimoto et al 2002) and Suzuki et al (Suzuki et al 1999) in their studies on the association between oxidative DNA damage and diabetes.…”

Section: Discussionsupporting

confidence: 90%

“…Lim et al (Lim et al 2000) clearly demonstrated that the frequency of oxidative mtDNA damage in the human skeletal muscle of end-stage renal disease (ESRD) patients was higher than in age-matched non--ESRD subjects and the increase in oxidative stress may lead to premature oxidative damage of the mitochondrial genome in diseased tissues. Suzuki et al (Suzuki et al 1999) reported that both the mtDNA deletion and the 8-OHdG levels correlated not only with age, but also with the duration of disease. In our previous study (Canakci et al 2006) and in this study we did not find the mtDNA deletion in the gingival tissues of healthy subjects in the age group <70 years.…”

Section: Discussionmentioning

confidence: 99%

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Increased salivary level of 8-hydroxydeoxyguanosine is a marker of premature oxidative mitochondrial DNA damage in gingival tissue of patients with periodontitis

Çanakçı

Tatar

et al. 2009

Arch. Immunol. Ther. Exp.

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Introduction: Oxidative stress may contribute to the pathogenesis of periodontitis. However, the detailed molecular mechanism remains unclear. Both 8-hydroxydeoxyguanosine (8-OHdG) and mitochondrial DNA (mtDNA) deletion have been reported as early oxidative DNA damage markers. In this study, 8-OHdG levels in saliva and mtDNA deletions in gingival tissue of patients with chronic periodontitis (CP) were evaluated. Materials and Methods: Gingival tissue and whole saliva samples were collected from 32 patients with CP and 32 healthy control subjects. To determine the clinical condition of each subject, the plaque index, gingival index, clinical attachment level (CAL), and probing depth (PD) were measured. Using the ELISA and polymerase chain reaction methods, the salivary 8-OHdG levels and the 7.4-kbp and 5-kbp mtDNA deletions were examined. Results: The 5-kbp mtDNA deletion was detected in 20 of the 32 periodontitis patients (62.5%), but was not detected in the healthy controls. The mean value of 8-OHdG in the saliva of the periodontitis patients with deleted mtDNA was significantly higher than in the patients with non-deleted mtDNA (p<0.01). Also, significant correlation was found between the occurrence of the 5-kbp mtDNA deletion and salivary 8-OHdG levels (p<0.01). Similar correlations were detected between salivary 8-OHdG levels and age, PD, and CAL (p<0.01, p<0.05). Conclusion: Increased oxidative stress may lead to premature oxidative DNA damage in the gingival tissue of periodontitis patients and the salivary 8-OHdG level may signify premature oxidative mtDNA damage in diseased gingival tissue.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Increased salivary level of 8-hydroxydeoxyguanosine is a marker of premature oxidative mitochondrial DNA damage in gingival tissue of patients with periodontitis

Çanakçı

Tatar

et al. 2009

Arch. Immunol. Ther. Exp.

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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: Discussionsupporting

confidence: 50%

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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“…Hyperglycemia, a well recognized pathogenetic factor of long-term complications in diabetes mellitus, not only generates more ROS but also attenuates antioxidative mechanisms through glycation of the scavenging enzymes. Therefore, oxidative stress has been considered to be a common pathogenic factor of diabetic complications [4][5][6] including nephropathy [7]. * Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

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

Yao

Weng

et al. 2004

Journal of Pharmaceutical and Biomedical Analysis

109

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Oxidative damage to mitochondrial DNA and its relationship to diabetic complications

Cited by 126 publications

References 22 publications

Increased salivary level of 8-hydroxydeoxyguanosine is a marker of premature oxidative mitochondrial DNA damage in gingival tissue of patients with periodontitis

Increased salivary level of 8-hydroxydeoxyguanosine is a marker of premature oxidative mitochondrial DNA damage in gingival tissue of patients with periodontitis

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

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

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