OXIDATIVE DAMAGE TO NUCLEAR DNA IN STREPTOZOTOCIN-DIABETIC RAT LIVER

Authors: Andican, Gülnur1; Burçak, Gülden1

Source: Clinical and Experimental Pharmacology and Physiology, Volume 32, Number 8, August 2005 , pp. 663-666(4)

Publisher: Blackwell Publishing

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Abstract:

SUMMARY

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-2prime-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-2prime-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/105 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.

Keywords: diabetes mellitus; oxidative DNA damage; 8-oxo-2prime-deoxyguanosine

Document Type: Original article

DOI: 10.1111/j.0305-1870.2005.04247.x

Affiliations: 1: Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey

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