A intervention study for improvement of decreased nitric oxide levels and oxidative stress in arsenosis patients in China

砷是一种自然存在的元素，在环境中无处不在。人类环境暴露的主要来源是通过饮用主要来自自然污染的含砷量高的水。在亚洲，数以百万计的人长期暴露在砷含量高的饮用水中，这些饮用水来自在富含砷的地质地层中钻探的井。一氧化氮（NO）是一种信使分子，在神经传递、血管舒张和免疫反应中起重要作用。在中国内蒙古慢性砷中毒流行地区的一项实地研究中，我们发现人体长期暴露于砷导致全身NO水平降低和氧化应激。在长期暴露于砷（18周，5μg/ml）的家兔中也发现了这种现象，这支持了砷是一种类金属的概念，它通过活性氧（ROS）的产生导致全身NO生成受损，增加氧化应激，降低抗氧化酶活性。虽然砷中毒的可逆性尚未确定，但用低砷水替代严重砷污染的饮用水被认为是砷中毒的潜在干预策略。然而，我们目前在内蒙古慢性砷中毒流行地区进行的干预研究表明，停止接触可以逆转砷中毒患者一氧化氮水平下降和周围血管疾病。这些结果对砷暴露的公共卫生方法具有重要意义。根据这些观察，我们认为在细胞水平上清除砷对减少砷中毒至关重要。

Arsenic is a naturally occurring element that is ubiquitously present in the environment. The main source of human environmental exposure is through consumption of water containing high levels of arsenic, primarily from natural contamination. In Asia, millions of people are chronically exposed to a high level of arsenic from their drinking water, obtained from wells drilled into arsenic-rich geologic strata. Nitric oxide (NO) is a messenger molecule that plays an important role in neurotransmission, vasodilation, and immune response. In a field study in an endemic area of chronic arsenic poisoning in Inner Mongolia, China, we found that prolonged exposure of humans to arsenic results in reduction of systemic NO levels and oxidative stress. Such phenomena were also seen with rabbits chronically exposed to arsenic (18 weeks, 5μg/ml), supporting the notion that arsenic is a metalloid that causes impairment of systemic NO production and increased oxidative stress through reactive oxygen species (ROS) generation and decreased antioxidant enzyme activities.Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is thought to be a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not been established. However, our current intervention study in the endemic area of chronic arsenic poisoning in Inner Mongolia indicated that decreased NO levels and peripheral vascular disease in arsenosis patients can be reversed by exposure cessation. These results have important implications in the public health approach to arsenic exposure. From these observations, we thought that clearance of arsenic at the cellular level is critical for decreased arsenic poisoning.