Gene Transfer of Cu/ZnSOD to Cerebral Vessels Prevents Subarachnoid Hemorrhage-induced Cerebral Vasospasm

The preventive effects of gene transfer of human copper/zinc superoxide dismutase (Cu/ZnSOD) on the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) were examined using a rat model of SAH. An experimental SAH was produced by injecting autologous arterial blood twice into the cisterna magna, and the changes in the diameter of the middle cerebral artery (MCA) were measured. Rats subjected to SAH exhibited a decreased diameter with an increased wall thickness of MCA that were significantly ameliorated by pretreatment with diphenyleneiodonium (DPI, 10microM), an inhibitor of NAD (P) H oxidase. Furthermore, application of recombinant adenovirus (100microliter of 1 x 1010 pfu/ml, intracisternally), which encodes human Cu/ZnSOD, 3 days before SAH prevented the development of SAH-induced vasospasm. Our findings demonstrate that SAH-induced cerebral vasospasm is closely related with NAD (P) H oxidase-derived reactive oxygen species, and these alterations can be prevented by the recombinant adenovirus-mediated transfer of human Cu/ZnSOD gene to the cerebral vasculature.

Effects of Cadmium on Superoxide Radical, Superoxide Dismutase, Catalase and ATPase Activity in Liver, Kidney and Testicle of Rats in Vtm and in Vivo / 예방의학회지

Production of free radicals of superoxide anion in tissues by cadmium, activities of superoxide dismutase and catalase to protect tissue damages caused by the free radicals and ATPase that plays an important role in energy metabolism at cellular level were investigated. Experiments in viro were conducted with liver, kidney and testicle tissue homogenates of rats adding 0.05~0.50 mM cadmium chloride, and in vivo experiments administering single dose of 5mg of cadmium/kg of body weight in 0.1% cadmium chloride solution intraperitoneally 48 hours prior to evisceration. Production of superoxide radicals in liver and testicle increased with addition of cadmium in vitro, but not in kidney. In vivo experiments, however superoxide radicals slightly increased in liver and kidney but not in testicle. Superoxide dismutase (Cu, Zn-SOD and Mn-SOD), catalase and ATPase (total, (Mg++)- & (Na+)- (K+)-) activity decreased in the presence of cadmium in dose dependent manner. Reduction of these enzyme activities varied not only with dosage of cadmium but also with type of tissue and between in vitro and in vivo experiment.