Inhibition of postcardiac arrest brain protein oxidation by acetyl-L-carnitine.
Free radical mediated, site-specific protein oxidation has been implicated in the pathophysiology of ischemia/reperfusion brain injury. The purpose of this study was to determine whether this form of molecular damage could be detected in a clinically relevant model employing 10-min cardiac arrest in dogs followed by restoration of spontaneous circulation for up to 24 h. The effects of postischemic acetyl-L-carnitine administration on protein oxidation were also tested due to its previously reported improvement of brain energy metabolism and neurological outcome in this model. Following the experimental period, soluble proteins were extracted from a sample of frontal cortex and reacted with dinitrophenylhydrazine for spectrophotometric measurement of protein carbonyl groups. The most important results of this study were that brain protein carbonyl groups were significantly elevated following 2 and 24 h of reperfusion compared to nonischemic controls, and that postischemic IV administration of acetyl-L-carnitine eliminated the increase in carbonyl groups observed at the 24-h period. These results indicate that brain protein oxidation does occur in a clinically relevant model of complete global cerebral ischemia and reperfusion, and that oxidation is inhibited under treatment conditions that improve neurological outcome.
Liu
Y
Y
Department of Biochemistry and Molecular Biology, George Washington University School of Medicine, Washington, DC 20037.
Rosenthal
R E
RE
Starke-Reed
P
P
Fiskum
G
G
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism; D004285:Dogs; D005260:Female; D005609:Free Radicals; D006323:Heart Arrest / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control
D005609:Free Radicals; D009419:Nerve Tissue Proteins; D000108:Acetylcarnitine