D-beta-hydroxybutyrate prevents glutamate-mediated lipoperoxidation and neuronal damage elicited during glycolysis inhibition in vivo.
Excitotoxic neuronal death mediated by over-activation of glutamate receptors has been implicated in ischemia, hypoglycemia and some neurodegenerative diseases. It involves oxidative stress and is highly facilitated during impairment of energy metabolism. We have shown previously that in vivo systemic glycolysis inhibition with iodoacetate (IOA), exacerbates glutamate excitotoxicity. We have now investigated whether this effect involves oxidative damage to membrane lipids, as evaluated by the presence of thiobarbituric acid-reactive substances. We have also tested whether the ketone body, D-beta-hydroxybutyrate (D-BHB), prevents lipoperoxidation and tissue damage. Results show that glutamate intrastriatal injection in control rats transiently enhances lipoperoxidation, while in IOA-treated animals increased lipoperoxidation is sustained. Treatment with D-BHB significantly reduces striatal lesions and lipoperoxidation. Vitamin E also reduced neuronal damage and lipoperoxidation. Results suggest that glycolysis impairment favors a pro-oxidant condition and situates oxidative damage as an important mediator of in vivo induced excitotoxicity. Results provide evidence for the neuroprotective effect of D-BHB against glutamate toxicity.
Mejía-Toiber
Jana
J
Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, AP 70-253, 04510, Mexico DF, Mexico.
Montiel
Teresa
T
Massieu
Lourdes
L
D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D007461:Iodoacetates / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017072:Neostriatum / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000477:Alkylating Agents; D000975:Antioxidants; D007461:Iodoacetates; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D018698:Glutamic Acid; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D020155:3-Hydroxybutyric Acid