Effect of Resveratrol on Oxidative Stress and Mitochondrial Dysfunction in Immature Brain during Epileptogenesis

Abstract

The presence of oxidative stress in immature brain has been demonstrated during the acute phase of status epilepticus (SE). The knowledge regarding the long periods of survival after SE is not unequivocal, lacking direct evidence. To examine the presence and time profile of oxidative stress, its functional effect on mitochondria and the influence of an antioxidant treatment in immature rats during epileptogenesis, status epilepticus (SE) was induced in immature 12-day-old rats by Li-pilocarpine and at selected periods of the epileptogenesis; rat pups were subjected to examinations. Hydroethidine method was employed for detection of superoxide anion (O2.−), 3-nitrotyrosine (3-NT), and 4-hydroxynonenal (4-HNE) for oxidative damage of mitochondrial proteins and complex I activity for mitochondrial function. Natural polyphenolic antioxidant resveratrol was given in two schemes: “acute treatment,” i.p. administration 30 min before, 30 and 60 min after induction of SE and “full treatment” when applications continued once daily for seven consecutive days (25 mg/kg each dose). The obtained results clearly document that the period of epileptogenesis studied (up to 4 weeks) in immature brain is associated with the significant enhanced production of O2.−, the increased levels of 3-NT and 4-HNE and the persisting deficiency of complex I activity. Application of resveratrol either completely prevented or significantly reduced markers both of oxidative stress and mitochondrial dysfunction. The findings suggest that targeting oxidative stress in combination with current antiepileptic therapies may provide a benefit in the treatment of epilepsy.

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Acknowledgments

This work was supported by grants #P303/10/0999 and #15-08565S from the Czech Science Foundation and with institutional support RVO: 6798523. The authors express their thanks to E. Lažková and V. Brožková for their excellent technical assistance.

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Correspondence to Jaroslava Folbergrová.

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Folbergrová, J., Ješina, P., Kubová, H. et al. Effect of Resveratrol on Oxidative Stress and Mitochondrial Dysfunction in Immature Brain during Epileptogenesis. Mol Neurobiol 55, 7512–7522 (2018). https://doi.org/10.1007/s12035-018-0924-0

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Keywords

  • Immature rats
  • Status epilepticus
  • Epileptogenesis
  • Oxidative stress
  • Mitochondrial dysfunction
  • Resveratrol
  • Protection