Age effect on brain pH during ischemia/reperfusion and pH influence on peroxidation.
Older gerbils are more sensitive to ischemia/reperfusion injury (IRI) than younger ones. Utilizing 31P-NMR to monitor in vivo pH and high energy phosphates of brain cortex undergoing an IRI showed that cortical intracellular pH decreased to 6.35 after ischemia and then increased with reperfusion, but older gerbils required significantly more time to recover than younger animals. Brain high energy phosphates dropped during ischemia but rebounded within 20 min reperfusion in younger gerbil brain but remained significantly lower in older gerbil brain for 50 min. These data suggest that IRI-induced brain acidification may enhance oxidative damage. In an in vitro system it was shown in both young and old brain homogenate that peroxidation rate increased when the pH of the incubation medium was decreased from 7.4 to 6.4. This was true in the presence or absence of an ADP/Fe/Ascorbate system in both young and old brain homogenate. Enhancement of peroxidation rate by ADP/Fe/Ascorbate addition was much more pronounced at pH 7.4 (30- to 40-fold increase) as compared to pH 6.4 (7.8- to 9.5-fold increase). This data can be interpreted to indicate that the lower pH makes endogenous Fe more available to catalyze oxidative damage. The fact that brain pH and high energy phosphates remain lower in older gerbil brains during IRI suggests that brain mitochondria from older animals are less capable of responding to a large oxidative stress brought on by an IRI.(ABSTRACT TRUNCATED AT 250 WORDS)
Funahashi
T
T
Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Floyd
R A
RA
Carney
J M
JM
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001923:Brain Chemistry / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D005849:Gerbillinae; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018384:Oxidative Stress; D010725:Phosphocreatine / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D007501:Iron; D001205:Ascorbic Acid