Effect of acetyl-L-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat--study by 13P- and 1H-NMR spectroscopy.
The effects of acetyl-L-carnitine (ALCAR) treatment on brain energy state recovery and lactic acid levels following 20 min ischemia and 2, 24 and 48 h reperfusion were investigated by 31P and 1H-NMR spectroscopy. Transient forebrain ischemia was induced by four-vessel occlusion method in fed 6-month-old Fischer rats. ALCAR or saline was administered by intraperitoneal route immediately after 20 min ischemia and again at 1, 4, 24 and 30 h during reperfusion. Twenty-min severe forebrain ischemia was associated with a marked decrease in phosphocreatine (PCr) and ATP levels and a corresponding increase in lactic acid, inorganic phosphate (Pi), AMP, creatine, glycerol 3-phosphate and alanine levels. Following reperfusion, a general tendency to restore pre-ischemic metabolite levels was observed. However, after 2 h reperfusion in saline-treated rats, lactic acid and Pi levels remained significantly higher, while ATP levels were still significantly lower than in non-ischemic controls. On the contrary, in ALCAR-treated animals a complete recovery of all metabolites including Pi and ATP was observed, while PCr levels were even more elevated compared with those in saline-treated rats. Furthermore lactic acid content was significantly lower than that in both saline-treated and non-ischemic control rats. It is concluded that a potential therapeutic role may be claimed for ALCAR in the treatment of cerebral ischemia through mechanisms that include faster recovery and improvement of brain energy production as well as a decreased lactic acid content during early post-ischemic reperfusion.
Institute for Research on Senescence, Sigma-Tau S.p.A., Pomezia, Italy.
T
T
Aureli
A
A
Miccheli
M E
ME
Di Cocco
O
O
Ghirardi
A
A
Giuliani
M T
MT
Ramacci
F
F
Conti
D000108:Acetylcarnitine / Q000494:pharmacology*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000409:Alanine / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005994:Glycerophosphates / Q000378:metabolism; D006859:Hydrogen; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D007773:Lactates / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D010710:Phosphates / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D015424:Reperfusion
D005994:Glycerophosphates; D007773:Lactates; D010710:Phosphates; D010725:Phosphocreatine; D010758:Phosphorus; D000249:Adenosine Monophosphate; D000108:Acetylcarnitine; D006859:Hydrogen; D000255:Adenosine Triphosphate; C029620:alpha-glycerophosphoric acid; D003401:Creatine; D000409:Alanine