Increased levels of circulating 8-oxodeoxyguanosine as a biomarker of sepsis severity in mice

In intensive care for sepsis, damage of intracellular environmental states is responsible for not only infectious disease severity but also oxidative DNA damage following hypometabolism such as hypoxia, hypotension, hypothermia, and hypoglycemia. Therefore, identification of a biomarker to monitor these intracellular equilibrium conditions is crucial for the prognosis of disease severity.

Under an environmental condition, the 8-oxodeoxyguanosine (8-OH-dG) levels in tissues were previously shown to be increased as a result of oxidative DNA damage. The purpose of this study was to elucidate whether the circulating 8-OH-dG levels may serve as a marker for severity in a mouse septic model.

Methods:
Thirty young male C57BL/6 mice were subjected to sepsis induction by cecal ligation and puncture (CLP), whereas 10 control mice without sepsis were used as the sham group.

Aspirated blood was obtained from either surviving mice at 72 h after sepsis induction or non-surviving mice at the time of death. The levels of circulating 8-OH-dG, serum lactate, and C-reactive protein (CRP) were determined by high-performance liquid chromatography.

These markers were analyzed for their ability to indicate severity by calculating the area under the receiver operating characteristic (ROC) curve.

Results:
The circulating 8-OH-dG levels, similar to the lactate levels, were significantly increased in the non-surviving group. The area under the ROC curve was 0.97 +/- 0.032 and 0.92 +/- 0.061 for 8-OH-dG and lactate, respectively, with the optimal threshold value to discriminate between the survivors and non-survivors being 1.3 (sensitivity, 80%; specificity, 100%) for 8-OH-dG and 14.1 (sensitivity, 70%; specificity, 80%) for lactate.

No significant change in CRP was observed between the two groups. Circulating 8-OH-dG levels better indicated severity than lactate and CRP concentrations, strongly implicating circulating 8-OH-dG in intracellular environmental conditions in a mouse septic model.

Conclusion:
The circulating 8-OH-dG levels may be a novel marker for evaluating disease severity during intensive care for sepsis.

Author: Jun-ichi HirataMunehiko OhyaToshiomi OkunoKeiji Kumon
Credits/Source: Journal of Intensive Care 2014, 2:41

Published on: 2014-07-03

News Provider: 7thSpace Interactive / EUPB Press Office

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