Oxidative stress in silicosis: kinetic clearance assay of tempo radicals.
Vallyathan-V; Leonard-S; Kuppusamy-P; Pack-D; Zhahan-M; Sanders-SP; Zweir-J
Toxicologist 1997 Mar; 36(1)(Part 2):109
A sensitive and specific kinetic clearance assay using low frequency electron in resonance (ESR) has been developed to facilitate investigations of the pathophysiological role of oxidative stress in lungs. Using this technique we investigated ROS' dependent kinetic clearance of instilled stable nitroxide radicals (TEMPO) in silicosis. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and lipid peroxidation were also studied in whole lungs of rats exposed to silica (quartz) and controls. The clearance of TEMPO followed first order kinetics showing significant differences in the rate for clearance between quartz vs sham exposed control lungs. Comparison of TEMPO clearance rates in the sham exposed controls and silicotic rats indicated an oxidative stress in the rats exposed to quartz. Studies of antioxidant enzymes SOD and GPx, in the lungs of quartz and sham exposed animals supported the oxidative stress and accelerated clearance of TEMPO by up regulated levels of enzymes in quartz exposed animals. Increased lipid peroxidation potential in the silicotics also supported a role for enhanced generation of ROS. These in vivo experiments directly demonstrate that silicotic lungs are in a state of oxidative stress and that increased generation of ROS is associated with enhanced levels of oxidative enzymes and lipid peroxldation. This technique offers great promise for the elucidation of ROS induced lung injury and development of therapeutic strategies for the prevention of damage.
Toxic-dose; Toxic-materials; Toxins; Exposure-assessment; Exposure-levels; Exposure-limits; Alveolar-cells; Lung-tissue; Lung-disorders; Lung-cells; Respiratory-system-disorders; Pulmonary-system-disorders; Laboratory-animals; Animal-studies; Animals; Silicosis; Quartz-dust; Silica-dusts
The Toxicologist. Society of Toxicology 36th Annual Meeting, March 9-13, 2006, Cincinnati, Ohio