Effect of D- and L-1,3-butanediol isomers on glycolytic and citric acid cycle intermediates in the rat brain.
DL-1,3-butanediol (DL-BD) is an ethanol dimer which affords cerebral protection in various experimental models of hypoxia and ischemia but its mechanism of action is unknown. DL-BD is a ketogenic alcohol and it has been proposed that its protective effect was accomplished through cerebral utilization of ketone bodies. Since DL-BD is a racemic, its metabolic effects could be due to D, L or both isomers. The effects of equimolar doses of DL-, D- and L-BD (25 mmol/Kg) on cerebral metabolism were studied by measuring the cortical levels of the main glycolytic (glycogen, glucose, glucose 6-phosphate, fructose 1,6-diphosphate, pyruvate and lactate) and citric acid cycle (citrate, alpha-ketoglutarate and L-malate) intermediates. The two BD isomers exerted different effects on cerebral metabolism. Unlike L-BD, D- and DL-BD treatments resulted in a slight (+10%) but significant increase in citrate level whereas L-BD treatment led to significant reduction in pyruvate (-12%) and lactate (-24%) levels. These effects were apparently not linked to hyperketonemia, since DL-BHB treatment, which mimicked hyperketonemia induced by DL-BD, had no effect on cerebral metabolites but might be due to intracerebral metabolism of BD.
Gueldry
S
S
Laboratoire de Pharmacodynamie, Faculté de Pharmacie, Dijon, France.
Bralet
J
J
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002072:Butylene Glycols / Q000097:blood / Q000633:toxicity*; D002245:Carbon Dioxide / Q000097:blood; D002952:Citric Acid Cycle / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects*; D007536:Isomerism; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002072:Butylene Glycols; D002245:Carbon Dioxide; C028491:1,3-butylene glycol