Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study.
Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study.
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DOI：
10.1159/000487639
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发表时间：
2018-05-01
期刊：
影响因子：
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通讯作者：
Sawa, Akira
中科院分区：
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作者：
Sedlak, Thomas W;Nucifora, Leslie G;Sawa, Akira
精神分裂症和其他神经精神障碍等待机制相关的干预。过量的氧化应激越来越多地被认为参与了脑部疾病的病理生理过程，多项研究报告了主要抗氧化剂谷胱甘肽(GSH)的减少。对于通过成像技术估计大脑中氧化应激相关变化的技术警告，导致研究人员探索外周GSH可能是氧化应激相关脑变化的病理标志。在GSH缺乏的临床前模型中，我们发现全脑和外周GSH水平之间存在相关性。我们发现，在每天口服7天后，自然产生的异硫氰酸酯萝卜硫醚提高了健康受试者的血液GSH水平。同时，我们通过7-T磁共振波谱研究了萝卜硫素对前扣带回皮质、海马区和丘脑GSH水平的潜在影响。观察到萝卜硫素治疗后和治疗前的血液和丘脑GSH比率之间存在显著的正相关，此外，治疗后脑组织GSH水平持续上升。这项临床先导性研究表明，探索外周GSH与临床/神经心理指标之间的关系的价值，以及萝卜硫素对神经精神疾病中改变的功能指标的影响。
Schizophrenia and other neuropsychiatric disorders await mechanism-associated interventions. Excess oxidative stress is increasingly appreciated to participate in the pathophysiology of brain disorders, and decreases in the major antioxidant, glutathione (GSH), have been reported in multiple studies. Technical cautions regarding the estimation of oxidative stress-related changes in the brain via imaging techniques have led investigators to explore peripheral GSH as a possible pathological signature of oxidative stress-associated brain changes. In a preclinical model of GSH deficiency, we found a correlation between whole brain and peripheral GSH levels. We found that the naturally occurring isothiocyanate sulforaphane increased blood GSH levels in healthy human subjects following 7 days of daily oral administration. In parallel, we explored the potential influence of sulforaphane on brain GSH levels in the anterior cingulate cortex, hippocampus, and thalamus via 7-T magnetic resonance spectroscopy. A significant positive correlation between blood and thalamic GSH post- and pre-sulforaphane treatment ratios was observed, in addition to a consistent increase in brain GSH levels in response to treatment. This clinical pilot study suggests the value of exploring relationships between peripheral GSH and clinical/neuropsychological measures, as well as the influences sulforaphane has on functional measures that are altered in neuropsychiatric disorders.