Increased Oxidative DNA Damage in Patients With Alcohol Dependence and Its Correlation With Alcohol Withdrawal Severity

Abstract

Chronic and excessive alcohol consumption enhances the formation of reactive oxygen species (ROS) and ethanol-derived free radicals. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a marker to estimate ROS-induced DNA damage. The study objective was to compare serum 8-OHdG levels between patients with alcohol dependence and healthy controls and to investigate the correlation between this marker and the severity of alcohol withdrawal syndrome (AWS). We recruited 79 patients with alcohol dependence and 63 healthy control subjects. The severity of AWS was evaluated using the Chinese version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar-C) every 8 hours. Levels of 8-OHdG, malondialdehyde (MDA), and other biologic indexes were assayed at baseline for patient and control groups, and after 1-week detoxification for the patient group. The 8-OHdG and MDA levels in the alcoholic group were significantly higher than those in the control group (0.34 vs. 0.27 ng/ml and 13.5 vs. 10.1 μM, respectively). Both 8-OHdG and MDA were significantly correlated with the highest CIWA-Ar-C (correlation coefficient = 0.39, p < 0.001 and 0.26, p = 0.02, respectively). In linear regression analysis, only 8-OHdG level was significantly correlated with the highest CIWA-Ar, but not MDA level (regression coefficient beta = 0.33, p = 0.003 and 0.17, p = 0.12, respectively). MDA, but not 8-OHdG levels, significantly decreased after 1 week of detoxification. These results indicate that our alcohol-dependent individuals are vulnerable to excessive production of free radicals. Notably, the oxidative DNA damage persisted after 1-week detoxification. The AWS severity was correlated with the increase in oxidative stress, particularly the 8-OHdG levels. The impact of sustained abstinence in alcoholic patients needs to be investigated in future studies.