Oxidative damage to nuclear DNA in streptozotocin-diabetic rat liver.
1. Accumulating evidence suggests that oxidative and glycative stress is enhanced in diabetes. Oxidative stress induces DNA damage. In the present study, we assessed the 8-oxo-2'-deoxyguanosine (8-oxodG) content of DNA, an indicator of oxidative DNA damage, in streptozotocin (STZ)-induced diabetic (n = 21) and control rats (n = 18). 2. Rats were rendered diabetic by intraperitoneal administration of STZ at a dose of 65 mg/kg. Glucose was determined by glucose oxidase and glycated haemoglobin (GHb), an indicator of glycative stress, was determined by agarose-boronate affinity chromatography. 8-Oxo-2'-deoxyguanosine within the DNA (ratio of 8-oxodG to deoxyguanosine (dG)) was assessed by HPLC in conjunction with both electrochemical (8-oxodG) and diode array (dG) detection. 3. Glucose, GHb and the extent of oxidative DNA damage in the liver of STZ-diabetic rats were much higher compared with control rats. There was a correlation between GHb and 8-oxodG/10(5) dG levels in control (r = 0.756, P < 0.001) and diabetic groups (r = 0.468, 0.02 < P < 0.05). 4. These results clearly show that oxidative damage to hepatic nuclear DNA increases in the diabetic state and that this increase is correlated with glycative stress.
Andican
Gülnur
G
Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. andican@e-kolay.net
Burçak
Gülden
G
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine