Effects of chronic sodium azide on brain and muscle cytochrome oxidase activity: a potential model to investigate environmental contributions to neurodegenerative diseases.
Deficits in oxidative phosphorylation have been implicated in many neurodegenerative diseases. In this study, cytochrome oxidase activity was inhibited following a 28-d systemic administration of nonlethal sodium azide via subcutaneous osmotic pumps. Quantitative enzyme histochemistry was performed on tissue sections from brain, skeletal muscle, and heart to localize cytochrome oxidase activity both globally and in regions within each tissue. Significant decreases of cytochrome oxidase activity were found in the brain and skeletal muscle but not heart. In addition, regions within each tissue were also analyzed, such as cortex and striatum in the brain and red and white fibers in skeletal muscle. The tissue specific inhibition of cytochrome oxidase by sodium azide could serve as a positive control for studies of other mitochondrial toxins in aerobically compromised cells. Therefore, chronic nonlethal sodium azide administration may provide a potential rat model for the study of mitochondrial dysfunction and the role of environmental pollutants in brain and muscle tissues affected in certain neurodegenerative diseases.
Berndt
J D
JD
Institute for Neuroscience and Center for Molecular and Cellular Toxicology, University of Texas at Austin, 78712, USA.
Callaway
N L
NL
Gonzalez-Lima
F
F
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors*; D006321:Heart / Q000187:drug effects; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019810:Sodium Azide / Q000494:pharmacology*; D014018:Tissue Distribution
D019810:Sodium Azide; D003576:Electron Transport Complex IV