Oxidative damage to DNA and its relationship with diabetic complications.

OBJECTIVE To detect the oxidative DNA damage in diabetic patients and to investigate the relationship of oxidative DNA damage with diabetes and diabetic nephropathy. METHODS Single cell gel electrophoresis (SCGE) was used to detect the DNA strand breaks in peripheral blood lymphocytes, and oxidative DNA damage product and serum 8-OHdG were determined by a competitive ELISA in 47 cases, including 25 patients without diabetic complications, 22 patients with diabetic nephropathy and 25 normal control subjects. RESULTS Diabetic patients showed greater oxidative damage to DNA. The percentage of comet cells and the length of DNA migration (comet tail length) of peripheral blood lymphocytes were significantly increased in patients with diabetes, and significantly higher in patients with diabetic nephropathy than in diabetic patients without vascular complications (P < 0.05). There was a significant increase in serum 8-OHdG in diabetic patients compared with normal subjects (P < 0.05). Moreover, serum 8-OHdG was much higher in patients with diabetic nephropathy than in diabetic patients without vascular complications (P < 0.05). CONCLUSION There is severe oxidative DNA damage in diabetic patients. Enhanced oxidative stress may be associated with diabetes, especially in patients with diabetic nephropathy.

[1]  Takeshi Matsumura,et al.  Evaluation of urinary 8-hydroxydeoxy-guanosine as a novel biomarker of macrovascular complications in type 2 diabetes. , 2003, Diabetes care.

[2]  E. Gerbino,et al.  Lipid hydroperoxide and markers of renal disease susceptibility in African‐Caribbean and Caucasian patients with Type 2 diabetes mellitus , 2001, Diabetic medicine : a journal of the British Diabetic Association.

[3]  P. Møller,et al.  Oxidative DNA damage in human white blood cells in dietary antioxidant intervention studies. , 2002, The American journal of clinical nutrition.

[4]  Y. Hinokio,et al.  Oxidative damage to mitochondrial DNA and its relationship to diabetic complications. , 1999, Diabetes research and clinical practice.

[5]  T. Hashimoto,et al.  Oxidative DNA Damage and Tubulointerstitial Injury in Diabetic Nephropathy , 2002, Nephron.

[6]  H. Utsumi,et al.  Oxidative stress measurement by in vivo electron spin resonance spectroscopy in rats with streptozotocin-induced diabetes , 1998, Diabetologia.

[7]  J. Hendry,et al.  Germ Cell and Dose-Dependent DNA Damage Measured by the Comet Assay in Murine Spermatozoaa after Testicular X-Irradiation1 , 2002, Biology of reproduction.

[8]  T. Lehtimäki,et al.  New biomarker evidence of oxidative DNA damage in patients with non‐insulin‐dependent diabetes mellitus , 1997, FEBS letters.

[9]  C. Richter.  Oxidative damage to mitochondrial DNA and its relationship to ageing. , 1995, The international journal of biochemistry & cell biology.

[10]  J. Baynes.  Role of Oxidative Stress in Development of Complications in Diabetes , 1991, Diabetes.

[11]  Y. Hinokio,et al.  Oxidative DNA damage in diabetes mellitus: its association with diabetic complications , 1999, Diabetologia.

[12]  U. Boggi,et al.  Functional and molecular defects of pancreatic islets in human type 2 diabetes. , 2005, Diabetes.

[13]  H. Nawata,et al.  Accumulation of 8-hydroxy-2'-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats. , 2002, Diabetes.

[14]  G. Lubec,et al.  Glycoxidation, and protein and DNA oxidation in patients with diabetes mellitus. , 1998, Clinical science.

[15]  T. Nicotera,et al.  Oxidative damage to DNA in diabetes mellitus , 1996, The Lancet.

[16]  G. King,et al.  Protein kinase C activation and the development of diabetic complications. , 1998, Diabetes.

[17]  Trevelyan Square,et al.  Recommendations for conducting the in vivo alkaline Comet assay , 2003 .

[18]  Y. Kaneda,et al.  Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage , 2000, Nature.

[19]  K. H. Kim,et al.  DNA damage in the kidneys of diabetic rats exhibiting microalbuminuria. , 1994, Free radical biology & medicine.

[20]  A. Young,et al.  Measurement of menadione-mediated DNA damage in human lymphocytes using the comet assay. , 1997, Free radical research.

[21]  R. Tice,et al.  Single cell gel/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing , 2000, Environmental and molecular mutagenesis.

[22]  A. Cerami,et al.  Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. , 1988, The New England journal of medicine.

[23]  A. Collins,et al.  Oxidative DNA damage, antioxidants and DNA repair: applications of the comet assay. , 2001, Biochemical Society transactions.

[24]  G. Paolisso,et al.  Oxidative Stress and Diabetic Vascular Complications , 1996, Diabetes Care.

[25]  D. Greene,et al.  Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. , 1987, The New England journal of medicine.