Department of Forensic Medicine, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Free Radic Biol Med. 2018 Oct;126:372-378. doi: 10.1016/j.freeradbiomed.2018.08.029. Epub 2018 Aug 23.
Elevated systemic oxidative stress levels of 8-oxoGuo and 8-oxodG have been reported in individuals with severe mental illness (SMI). As no previous studies have addressed the link between local levels of 8-oxoGuo and 8-oxodG in the central nervous system (CNS), measured in cerebrospinal fluid (CSF), and urinary systemic levels, we employed autopsy-based material to elucidate this aspect. Additionally, we investigated the impact of 8-oxoGuo and 8-oxodG levels on the prevalence of somatic co-morbidities. Based on post mortem samples from deceased individuals with SMI (N = 107), we found significantly elevated urinary levels of both 8-oxoGuo and 8-oxodG compared to mentally healthy living controls. While we found an association between urinary and CSF 8-oxodG levels (r = 0.50, P < 0.001), a similar correlation was not evident for 8-oxoGuo (r = 0.15, P = 0.16). Additionally, the two r-values were significantly different (P < 0.001). Neither marker in urine or CSF was associated with obesity-related variables, metabolic syndrome or type 2 diabetes. The post mortem interval did not affect the results, but the agonal phase seemingly introduced bias. This study provided novel insights into the cellular oxidative stress levels in individuals with SMI. We demonstrated that increased oxidative stress locally and systemically is correlated and is a clear phenomenon in SMI. Although post mortem measurements contain some weaknesses, our study indicates DNA as the main site of oxidative stress modifications in the CNS in SMI. This may provide novel opportunities for treatment modalities. Additionally, our study demonstrated the applicability of post mortem material investigating systemic and local 8-oxoGuo and 8-oxodG levels.
有研究报道，严重精神疾病（SMI）患者的全身氧化应激水平升高，表现为 8-氧鸟嘌呤和 8-氧脱氧鸟苷（8-oxodG）升高。由于之前没有研究探讨中枢神经系统（CNS）脑脊液（CSF）和尿液中局部 8-氧鸟嘌呤和 8-氧脱氧鸟苷（8-oxodG）水平与全身系统水平之间的联系，我们利用尸检材料来阐明这一方面。此外，我们还研究了 8-氧鸟嘌呤和 8-氧脱氧鸟苷水平对躯体共病患病率的影响。基于 SMI 死亡患者的尸检样本（N=107），我们发现与心理健康的对照组相比，尿液中 8-氧鸟嘌呤和 8-氧脱氧鸟苷的水平显著升高。虽然我们发现尿液和 CSF 中 8-氧脱氧鸟苷水平之间存在关联（r=0.50，P<0.001），但 8-氧鸟嘌呤则没有明显相关性（r=0.15，P=0.16）。此外，两个 r 值差异显著（P<0.001）。尿液或 CSF 中的两种标志物均与肥胖相关变量、代谢综合征或 2 型糖尿病无关。尸检间隔时间不影响结果，但濒死期似乎会产生偏差。本研究为 SMI 患者的细胞氧化应激水平提供了新的见解。我们证明了局部和全身氧化应激水平增加是相关的，这是 SMI 中的一个明显现象。尽管尸检测量存在一些局限性，但我们的研究表明，氧化应激修饰的主要部位是 CNS 中的 DNA，这可能为治疗方法提供新的机会。此外，我们的研究还表明，利用尸检材料研究全身和局部 8-氧鸟嘌呤和 8-氧脱氧鸟苷水平是可行的。
