Decreased Nitric Oxide Production in the Rat Brain after Chronic Arsenic Exposure
Decreased Nitric Oxide Production in the Rat Brain after Chronic Arsenic Exposure
复制标题
DOI：
10.1007/s11064-006-9118-7
复制
发表时间：
2006-07
影响因子：
4.4
通讯作者：
S. Zarazúa;F. Pérez-Severiano;J. M. Delgado;Luz M Martínez;D. Ortiz-Pérez;M. Jiménez-Capdeville
中科院分区：
文献类型：
--
作者：
S. Zarazúa;F. Pérez-Severiano;J. M. Delgado;Luz M Martínez;D. Ortiz-Pérez;M. Jiménez-Capdeville
慢性砷暴露与神经系统损害、血管疾病、肝脏和肾脏损害以及不同类型的癌症有关。砷暴露后，检测到外周一氧化氮（NO）的改变，我们在这里探讨了大脑中NO的产生。雌性Wistar大鼠从妊娠期、哺乳期至4月龄，在饮水中接触亚砷酸盐（4 ~ 5 mg/kg/d）。体外测定纹状体NOS活性、NO代谢物含量、活性氧生成（ROS）和脂质过氧化（LPx），并通过微透析法测定瓜氨酸在体内的NO生成。暴露动物对NMDA受体刺激的反应明显降低，纹状体中NOS活性降低，亚硝酸盐和硝酸盐水平下降。这些NO功能标记伴随着显著升高的LPx和ROS的产生。这些结果提供了与砷暴露有关的大鼠脑NO功能障碍的证据。
Chronic arsenic exposure is associated with nervous system damage, vascular disease, hepatic and renal damage as well as different types of cancer. Alterations of nitric oxide (NO) in the periphery have been detected after arsenic exposure, and we explored here NO production in the brain. Female Wistar rats were exposed to arsenite in drinking water (4–5 mg/kg/day) from gestation, lactation and until 4 months of age. NOS activity, NO metabolites content, reactive oxygen species production (ROS) and lipid peroxidation (LPx) were determined in vitro in the striatum, and NO production was estimated in vivo measuring citrulline by microdialysis. Exposed animals showed a significantly lower response to NMDA receptor stimulation, reduction of NOS activity and decreased levels of nitrites and nitrates in striatum. These markers of NO function were accompanied by significantly higher levels of LPx and ROS production. These results provide evidence of NO dysfunction in the rat brain associated with arsenic exposure.