Original articleThe evaluation of oxidative DNA damage in children with brain damage using 8-hydroxydeoxyguanosine levels☆
Introduction
Reactive oxygen intermediates can damage various biomolecules in humans, such as DNA, lipids, and proteins [1], [2]. Biomarkers for DNA damage by oxidative stress include 8-hydroxydeoxyguanosine (8-OHdG), an enzyme that repairs damaged DNA and is excreted to urine [2], [3]. Currently, 8-OHdG is used as a sensitive marker for oxidative DNA damage [4], [5], [6]. It has been reported that oxidative stress accelerates brain tissue damage at the early phase of certain pathological processes such as cerebrovascular injury, brain edema, and meningeal inflammation [7], [8], [9]. Previously, we reported the time course of urinary 8-OHdG levels in adults with chronic arsenic poisoning, and suggested the clinical utility of urinary 8-OHdG to assess the recovery from DNA damage [10]. Few studies have analyzed urinary or CSF 8-OHdG levels in children with organic brain damage [7], [11], [12]. In the present study, we compared urinary and CSF 8-OHdG levels in children with probable brain damage with those of healthy children in order to determine whether urinary 8-OHdG level can be used as a reliable marker of oxidative stress in brain-damaged children.
Section snippets
Patients and methods
All of this research received prior approval from the university institutional review body (Nos. 697, 738), and informed consent was obtained from the parents of each patient. We measured urinary and CSF 8-OHdG levels using the samples remaining after the routine diagnostic examinations.
The concentration of 8-OHdG in urine samples from children with brain damage
The mean ± SD concentration of 8-OHdG in the healthy control children (n = 51, aged 0–15 years) was 18.9 ± 8.50 ng/mg cr. The urinary 8-OHdG concentrations in children with brain damage are shown in Table 1. The levels in children with SE averaged 2 times higher than that in healthy children, but this difference was not statistically significant (Fig. 1). The mean concentration of 8-OHdG in urine samples of HIE patients and CNS infections was significantly higher than that in control subjects (Fig. 2,
8-OHdG in childhood disease
Currently, the influence of oxidative stress that occurs in various disorders is estimated using a reactive oxygen species (ROS) modulator, active oxygen erasing system enzymatic antioxidants, or genetic transcription factors. In this study, we measured 8-OHdG to estimate oxidative stress in vivo. 8-OHdG is widely used as a biomarker of oxidative DNA damage [2], [5], [6], [10]. A few groups have identified high levels of 8-OHdG in the CSF of patients with Alzheimer’s disease and Parkinson’s
Conclusion
This study examined 8-OHdG levels in childhood CNS disorders using CSF and urine samples. Our results suggest that oxidative stress plays an important role in brain damage in children and correlates with the disease state. CSF 8-OHdG reflects active oxidative stress-induced brain injury in children more closely than urinary 8-OHdG. On the other hand, urinary 8-OHdG is thought to be useful as a clinical marker due to its simple and non-invasive collection compared with CSF 8-OHdG. Urinary 8-OHdG
Acknowledgements
The authors greatly appreciate the expert advices and helpful suggestions of Eishi Asano, MD, PhD, MS, Anannit Visudtibhan, MD, Andrew L. Lux, MD, Tilman Ruff, MD, PhD and Shinobu Tatsunami, PhD. We also thank MC medical, Inc. for technical support for the measurement of CSF 8-OHdG levels and Mitsubishi Pharma Corporation for the great support.
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This work was supported in part by funding from the Grant-in-Aid 15406030 (to H. Yamauchi) for scientific research from the Ministry of Education, Culture, Sport, and Technology.