Influence of ketone bodies on oxidative stress parameters in brain of developing rats in vitro.
Pro-oxidant and antioxidant properties have been found for acetoacetate (AcAc) and beta-hydroxybutyrate (BHB) in peripheral tissues. In the present study we investigated the role of AcAc and BHB at concentrations found in diabetic patients during ketoacidotic crises and in individuals affected by succinyl CoA: 3-oxoacid CoA transferase and acetoacetyl-CoA thiolase deficiencies, disorders clinically characterized by neurological symptoms, on a large number of oxidative stress parameters in fresh cerebral cortex of developing rats. Lipid peroxidation (chemiluminescence and thiobarbituric acid-reactive substances levels), protein oxidative damage (carbonyl formation and sulfhydryl oxidation), 2',7'-dichlorofluorescin diacetate oxidation and the non-enzymatic (total antioxidant reactivity and glutathione levels) and enzymatic (glutathione peroxidase, superoxide dismutase and catalase activities) antioxidant defenses were not changed by doses of BHB and AcAc as high as 25 mM in cortical supernatants under basal conditions. Furthermore, BHB did not affect the increased thiobarbituric acid-reactive substances levels provoked by 3-hydroxy-3-methylglutaric and 3-methylglutaconic acids and by a hydroxyl-induced generation system. Finally, BHB and AcAc were not able to oxidize sulfhydryl groups from a commercial GSH solution. Therefore, under basal conditions or under situations with high production of free radicals, AcAc and BHB were not able to reduce or increase the oxidative stress parameters in the brain. Taken together, our present results do not support the hypothesis that BHB and AcAc act as potent direct or indirect pro-oxidants or antioxidants in the CNS.
Beskow
Ana Paula
AP
Universidade Luterana do Brasil, Canoas, Brazil.
Fernandes
Carolina Gonçalves
CG
Leipnitz
Guilhian
G
da Silva
Lucila de Bortoli
Lde B
Seminotti
Bianca
B
Amaral
Alexandre U
AU
Wyse
Angela T S
AT
Wannmacher
Clóvis M D
CM
Vargas
Carmen R
CR
Dutra-Filho
Carlos S
CS
Wajner
Moacir
M
D020155:3-Hydroxybutyric Acid / Q000378:metabolism*; D000090:Acetoacetates / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D005452:Fluoresceins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D050050:Protein Carbonylation / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000090:Acetoacetates; D000975:Antioxidants; D005452:Fluoresceins; D007657:Ketone Bodies; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C029569:diacetyldichlorofluorescein; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D020155:3-Hydroxybutyric Acid
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