Neurochemical Research

, Volume 28, Issue 12, pp 1793–1797 | Cite as

Ketogenic Diet Increases Glutathione Peroxidase Activity in Rat Hippocampus

  • Denize R. Ziegler
  • Leticia C. Ribeiro
  • Martine Hagenn
  • lonara R. Siqueira
  • Emeli Araújo
  • Iracy L. S. Torres
  • Carmem Gottfried
  • Carlos Alexandre Netto
  • Carlos-Alberto Gonçalves


Ketogenic diets have been used in the treatment of refractory childhood epilepsy for almost 80 years; however, we know little about the underlying biochemical basis of their action. In this study, we evaluate oxidative stress in different brain regions from Wistar rats fed a ketogenic diet. Cerebral cortex appears to have not been affected by this diet, and cerebellum presented a decrease in antioxidant capacity measured by a luminol oxidation assay without changes in antioxidant enzyme activities—glutathione peroxidase, catalase, and superoxide dismutase. In the hippocampus, however, we observed an increase in antioxidant activity accompanied by an increase of glutathione peroxidase (about 4 times) and no changes in lipoperoxidation levels. We suggest that the higher activity of this enzyme induced by ketogenic diet in hippocampus might contribute to protect this structure from neurodegenerative sequelae of convulsive disorders.

Ketogenic diet oxidative stress glutathione peroxidase lipoperoxidation hippocampus 


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  1. 1.
    Castagne, V., Gautschi, M., Lefevre, K., Posada, A., and Clarke, P. G. H. 1999. Relationships between neuronal death and the cellular redox status: Focus on the developing nervous system. Prog. Neurobiol. 59:397-423.Google Scholar
  2. 2.
    Coyle, J. T. and Puttfarcken, P. 1993. Oxidative stress, glutamate, and neurodegenerative disorders. Science 262:689-695.Google Scholar
  3. 3.
    Halliwell, B. and Gutteridge, J. M. C. 1999. Free radicals in biology and medicine. Pages 721-731, in Halliwell, B. and Gutteridge, J. M. C. (eds.), Oxidative stress and disorders of the nervous system: General principles, Oxford University Press, New York.Google Scholar
  4. 4.
    Pazdernik, T. L., Layton, M., Nelson, S. R., and Samson, F. E. 1992. The osmotic/calcium stress theory of brain damage: Are free radicals involved? Neurochem. Res. 17:11-21.Google Scholar
  5. 5.
    Willmore, L. J. 1990. Post-traumatic epilepsy: Cellular mechanisms and implications for treatment. Epilepsia 31:S67-S73.Google Scholar
  6. 6.
    Brigelius-Flohe, R. 1999. Tissue-specific functions of individual glutathione peroxidase, Free Radic. Biol. Med. 27:951-965.Google Scholar
  7. 7.
    Dringen, R. 2000. Metabolism and functions of glutathione in brain. Prog. Neurobiol, 62:649-671.Google Scholar
  8. 8.
    Swink, T. D., Vining, E. P. G., and Freeman, J. M. 1997. The ketogenic diet. Adv. Pediat. 44:297-329.Google Scholar
  9. 9.
    Vining, E. P. G. 1999. Clinical efficacy of the ketogenic diet. Epilepsy Res. 37:181-190.Google Scholar
  10. 10.
    Ziegler, D. R., Araújo, E., Rotta, L., Perry, L. M., and Gonçalves, C. A. 2002. ketogenic diet increases protein phosphorylation in brain slices of rats. J. Nutr. 132:483-487.Google Scholar
  11. 11.
    Fraga, C. G., Leibovitz, B. E., and Tappel, A. L. 1988. Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slice: Characterization and comparison with homogenates and microsomes. Free Radic. Biol. Med. 4:155-161.Google Scholar
  12. 12.
    Lissi, E., Salim-hanna, M., Pascual, C., and del Castilho, M. D. 1995. Evaluation of total antioxidant potential (TRAP) and total antioxidant reactivity (TAR) from luminol-enhanced chemiluminescence measurements. Free Radic. Biol. Med. 18:153-158.Google Scholar
  13. 13.
    Desmarchelier, C., Barros, S., Repetto, M., Latorre, L. R., Kato, M., Coussio, J., and Ciccia, G. 1997. 4-Nerolidylcatechol from Pothomorphe spp. scavenges peroxyl radicals and inhibits Fe(II)-dependent DNA damage. Planta Med. 63:561-563.Google Scholar
  14. 14.
    Aebi, H. 1984. Catalase in vitro. Methods Enzymol. 105:121-126.Google Scholar
  15. 15.
    Wendel, A. 1981. Glutathione peroxidase. Methods Enzymol. 77:325-332.Google Scholar
  16. 16.
    Lowry, O H., Rosenbrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265-275.Google Scholar
  17. 17.
    Kim, S. K. 1999. National Institutes of Health workshop: Role of nutrient regulation of signal transduction in metabolic diseases. Am. J. Clin. Nutr. 70:544-571.Google Scholar
  18. 18.
    Arnaiz, S. L., Travacio, M., Llesuy, S., and Arnaiz, G. R. L. 1998. Regional vulnerability to oxidative stress in a model of experimental epilepsy. Neurochem. Res. 23:1477-1483.Google Scholar
  19. 19.
    Candelario-Jalil, E., Al-Dalain, S. M., Castillo, R., Martinez, G., and Fernandez, O. S. 2001. Selective vulnerability to kainate-induced oxidative damage in different rat brain regions. J. Appl. Toxicol. 21:403-407.Google Scholar
  20. 20.
    Homi, H. M., Freitas, J. J., Curi, R., Velasco, I. T., and Junior, B. A. 2002. Changes in superoxide dismutase and catalase activities of rat brain regions during early global transient ischemia/reperfusion. Neurosci. Lett. 333:37-40.Google Scholar
  21. 21.
    Choi, B. H. 1993. Oxygen, antioxidants and brain dysfunction. Yonsei Med. J. 34:1-10.Google Scholar
  22. 22.
    Sinet, P. M., Heikkila, R. E., and Cohen, G. 1980. Hydrogen peroxide production in rat brain in vivo. J. Neurochem. 34:1421-1428.Google Scholar
  23. 23.
    Sato, N., Shimizu, H., Shimomura, Y., Suwa, K., and Kobayashi, I. 1992. Mechanism of inhibitory action of ketone bodies on the production of reactive oxygen intermediates (ROIS) by polymorphonuclear leukocytes. Life Sci. 51:113-118.Google Scholar
  24. 24.
    Jain, S. K. and McVie, R. 1999. Hyperketonemia can increase lipid peroxidation and lower glutathione levels in human erythrocytes in vitro and in type 1 diabetic patients. Diabetes 48:1850-1855.Google Scholar
  25. 25.
    Jain, S. K., Kannan, K., and Lim, G. 1998. Ketosis (acetoacetate) can generate oxygen radicals and cause increased lipid peroxidation and growth inhibition in human endothelial cells. Free Radic. Biol. Med. 25:1083-1088.Google Scholar
  26. 26.
    Herrero, A., Portero-Otin, M., Bellmunt, M. J., Pamplona, R., and Barja, G. 2001. Effect of the degree of fatty acid unsaturation of rat heart mitochondria on their rates of H2O2 production and lipid and protein oxidative damage. Mech. Ageing Dev. 122:421-443.Google Scholar
  27. 27.
    Ntambi, J. M. and Bene, H. 2001. Polyunsaturated fatty acid regulation of gene expression. J. Mol. Neurosci. 16:273-8001.Google Scholar
  28. 28.
    Schwartzkroin, P. 1999. Mechanisms underlying the anti-epileptic efficacy of the ketogenic diet. Epilepsy Res. 37:171-180.Google Scholar
  29. 29.
    Weber, G. F., Maertens, P., Meng, X. Z., and Pippenger, C. E. 1991. Glutathione peroxidase deficiency and childhood seizures Comment. Lancet 15:1443-1444.Google Scholar
  30. 30.
    Bellissimo, M. I., Amado, D., Abdalla, D. S., Ferreira, E. C., Cavalheiro, E. A., and Naffah-Mazzacoratti, M. G. 2001. Superoxide dismutase, glutathione peroxidase activities and the hydroperoxide concentration are modified in the hippocampus of epileptic rats. Epilepsy Res. 46:121-128.Google Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Denize R. Ziegler
    • 1
  • Leticia C. Ribeiro
    • 2
  • Martine Hagenn
    • 3
  • lonara R. Siqueira
    • 2
  • Emeli Araújo
    • 2
  • Iracy L. S. Torres
    • 2
  • Carmem Gottfried
    • 1
    • 2
  • Carlos Alexandre Netto
    • 2
  • Carlos-Alberto Gonçalves
    • 2
  1. 1.Centro de Ciências da SaúdeUniversidade do Vale do Rio dos SinosSão Leopoldo, RSBrazil
  2. 2.Departamento de Bioquìmica, ICBSUniversidade Federal do Rio Grande do SulPorto Alegre, RSBrazil
  3. 3.Departamento de Fisiologia, ICBSUniversidade Federal do Rio Grande do SulPorto Alegre, RSBrazil

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