title: Protection of hypoglycemia-induced neuronal death by β-hydroxybutyrate involves the preservation of energy levels and decreased production of reactive oxygen species.
abstract: Glucose is the main energy substrate in brain but in certain circumstances such as prolonged fasting and the suckling period alternative substrates can be used such as the ketone bodies (KB), beta-hydroxybutyrate (BHB), and acetoacetate. It has been shown that KB prevent neuronal death induced during energy limiting conditions and excitotoxicity. The protective effect of KB has been mainly attributed to the improvement of mitochondrial function. In the present study, we have investigated the protective effect of D-BHB against neuronal death induced by severe noncoma hypoglycemia in the rat in vivo and by glucose deprivation (GD) in cortical cultures. Results show that systemic administration of D-BHB reduces reactive oxygen species (ROS) production in distinct cortical areas and subregions of the hippocampus and efficiently prevents neuronal death in the cortex of hypoglycemic animals. In vitro results show that D-BHB stimulates ATP production and reduces ROS levels, while the nonphysiologic isomer of BHB, L-BHB, has no effect on energy production but reduces ROS levels. Data suggest that protection by BHB, not only results from its metabolic action but is also related to its capability to reduce ROS, rendering this KB as a suitable candidate for the treatment of ischemic and traumatic injury.
authors: División de Neurociencias, Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), México DF, México.
authors: Alberto
authors: A
authors: Julio-Amilpas
authors: División de Neurociencias, Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), México DF, México.
authors: Teresa
authors: T
authors: Montiel
authors: División de Neurociencias, Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), México DF, México.
authors: Eva
authors: E
authors: Soto-Tinoco
authors: División de Neurociencias, Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), México DF, México.
authors: Cristian
authors: C
authors: Gerónimo-Olvera
authors: División de Neurociencias, Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), México DF, México.
authors: Lourdes
authors: L
authors: Massieu
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000090:Acetoacetates / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007003:Hypoglycemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007657:Ketone Bodies / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000090:Acetoacetates; D007657:Ketone Bodies; D017382:Reactive Oxygen Species; C016635:acetoacetic acid; D000255:Adenosine Triphosphate; D005947:Glucose; D020155:3-Hydroxybutyric Acid
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