Assessing Free-Radical-Mediated DNA Damage during Cardiac Surgery: 8-Oxo-7,8-dihydro-2'-deoxyguanosine as a Putative Biomarker

Linda Turnu, Alessandro Di Minno, Benedetta Porro, Isabella Squellerio, Alice Bonomi, Chiara Maria Manega, José Pablo Werba, Alessandro Parolari, Elena Tremoli, Viviana Cavalca, Linda Turnu, Alessandro Di Minno, Benedetta Porro, Isabella Squellerio, Alice Bonomi, Chiara Maria Manega, José Pablo Werba, Alessandro Parolari, Elena Tremoli, Viviana Cavalca

Abstract

Coronary artery bypass grafting (CABG), one of the most common cardiac surgical procedures, is characterized by a burst of oxidative stress. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), produced following DNA repairing, is used as an indicator of oxidative DNA damage in humans. The effect of CABG on oxidative-induced DNA damage, evaluated through the measurement of urinary 8-oxodG by a developed and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in 52 coronary artery disease (CAD) patients, was assessed before (T0), five days (T1), and six months (T2) after CABG procedure. These results were compared with those obtained in 40 subjects with cardiovascular risk factors and without overt cardiovascular disease (CTR). Baseline (T0) 8-oxodG was higher in CAD than in CTR (p = 0.035). A significant burst was detected at T1 (p = 0.019), while at T2, 8-oxodG levels were significantly lower than those measured at T0 (p < 0.0001) and comparable to those found in CTR (p = 0.73). A similar trend was observed for urinary 8-iso-prostaglandin F2α (8-isoPGF2α ), a reliable marker of oxidative stress. In the whole population baseline, 8-oxodG significantly correlated with 8-isoPGF2α levels (r = 0.323, p = 0.002). These data argue for CABG procedure in CAD patients as inducing a short-term increase in oxidative DNA damage, as revealed by 8-oxodG concentrations, and a long-term return of such metabolite toward physiological levels.

Figures

Figure 1
Figure 1
Representative chromatogram of 8-oxodG and of its internal standard 15N5-8-oxodG in urine pool sample.
Figure 2
Figure 2
Levels of 8-oxodG measured in urine from CAD patients and CTR subjects. Data are represented as mean ± SD. Comparisons between groups were performed by covariance analysis, adjusting for age and sex.
Figure 3
Figure 3
Time course of 8-oxodG (a) and of 8-isoPGF2α (b) following CABG surgery. Data are represented as mean ± SD.
Figure 4
Figure 4
Correlation between baseline levels of 8-oxodG and 8-iso-PGF2α in the whole population analyzed (n = 92).

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