Hussain S, Rodgers D A, Duhart H M, Ali S F
Neurochemistry Laboratory, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA.
J Environ Sci Health B. 1997 May;32(3):395-409. doi: 10.1080/03601239709373094.
The present study was undertaken to determine if in vitro exposure to mercuric chloride produces reactive oxygen species (ROS) in the synaptosomes prepared from various regions of rat brain. The effects of in vivo exposure to mercury on antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in different regions of rat brain were also investigated. Adult male Sprague-Dawley (CD) rats were dosed with 0, 1, 2.0 or 4.0 mg HgCl2/kg body weight, for 7 days. One week after the last dose, animals were sacrificed by decapitation, their brains were removed and dissected and frozen in dry ice prior to measuring the activities of these enzymes. The results demonstrated that in vitro exposure to mercury produced a concentration-dependent increase of ROS in different regions of the rat brain. In vivo exposure to mercury produced a significant decrease of total SOD, Cu, Zn-SOD and Mn-SOD activities in the cerebellum of rats treated with different doses of mercury. SOD activity did not vary significantly in cerebral cortex and brain stem. GPx activity declined in a dose-dependent manner in the cerebellum with a significant reduction in animals receiving the 4 mg HgCl2/kg body weight. The activity of GPx increased in the brain stem while unchanged in the cerebral cortex. The results demonstrate that inorganic mercury decreased SOD activity significantly in the cerebellum while GPx activity was affected in both cerebellum and brain stem. Therefore, it can be concluded that oxidative stress may contribute to the development of neurodegenerative disorders caused by mercury intoxication.
本研究旨在确定体外暴露于氯化汞是否会在从大鼠脑不同区域制备的突触体中产生活性氧(ROS)。还研究了体内暴露于汞对大鼠脑不同区域抗氧化酶如超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)活性的影响。成年雄性Sprague-Dawley(CD)大鼠分别给予0、1、2.0或4.0mg HgCl2/kg体重,持续7天。最后一次给药一周后,通过断头处死动物,取出大脑并进行解剖,在测量这些酶的活性之前在干冰中冷冻。结果表明,体外暴露于汞会使大鼠脑不同区域的ROS呈浓度依赖性增加。体内暴露于汞会使不同剂量汞处理的大鼠小脑中总SOD、铜锌超氧化物歧化酶(Cu,Zn-SOD)和锰超氧化物歧化酶(Mn-SOD)活性显著降低。大脑皮层和脑干中的SOD活性没有显著变化。小脑中的GPx活性呈剂量依赖性下降,接受4mg HgCl2/kg体重的动物中显著降低。脑干中的GPx活性增加,而大脑皮层中则保持不变。结果表明,无机汞显著降低了小脑中的SOD活性,而GPx活性在小脑和脑干中均受到影响。因此,可以得出结论,氧化应激可能促成汞中毒引起的神经退行性疾病的发展。