D-serine induces lipid and protein oxidative damage and decreases glutathione levels in brain cortex of rats.
The present work investigated the in vitro effects of D-serine (D-Ser) on important parameters of oxidative stress in cerebral cortex of young rats. Our results show that D-Ser significantly induced lipid peroxidation, as determined by increase of thiobarbituric acid-reactive substances and chemiluminescence levels, as well as protein oxidative damage since carbonyl formation and sulfhydryl oxidation were enhanced by this amino acid. Furthermore, the addition of free radical scavengers significantly prevented D-Ser-induced lipid oxidative damage, suggesting that free radicals were involved in this effect. D-Ser also significantly diminished glutathione levels in cortical supernatants, decreasing therefore the major brain antioxidant defense. Finally, D-Ser oxidized a glutathione commercial solution in a medium devoid of brain supernatants, indicating that it behaved as a direct acting oxidant. In contrast, L-serine, L-alanine and L-threonine at concentrations as high as 5 mM did not significantly change chemiluminescence values, carbonyl content and GSH concentrations, implying a selective effect for D-serine. However, cortical supernatants exposed to 5 mM L-serine for different periods resulted in a gradual enhancement of TBA-RS levels as pre-incubation time increased. The present data indicate that D-Ser induces oxidative stress in cerebral cortex of young rats. Therefore, it is presumed that this mechanism may be involved at least in part in the neurological damage found in patients affected by disorders in which D-Ser metabolism is compromised, leading to altered concentrations of this D-amino acid.
da Silva
Lucila de Bortoli
Lde B
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Leipnitz
Guilhian
G
Seminotti
Bianca
B
Fernandes
Carolina G
CG
Beskow
Ana Paula
AP
Amaral
Alexandre U
AU
Wajner
Moacir
M
D000409:Alanine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D049449:Luminescence; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013912:Threonine / Q000494:pharmacology
D000975:Antioxidants; D016877:Oxidants; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D013912:Threonine; D012694:Serine; D005978:Glutathione; D000409:Alanine