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Neurotoxicity Research

, Volume 32, Issue 3, pp 368–380 | Cite as

Evaluation of the Protective Effects of Sarains on H2O2-Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Neuroblastoma Cells

  • Rebeca Alvariño
  • Eva Alonso
  • Marie-Aude Tribalat
  • Sandra Gegunde
  • Olivier P. Thomas
  • Luis M. Botana
ORIGINAL ARTICLE

Abstract

Sarains are diamide alkaloids isolated from the Mediterranean sponge Haliclona (Rhizoniera) sarai that have previously shown antibacterial, insecticidal and anti-fouling activities. In this study, we examined for the first time the neuroprotective effects of sarains 1, 2 and A against oxidative stress in a human neuronal model. SH-SY5Y cells were co-incubated with sarains at concentrations ranging from 0.01 to 10 μM, and the well-known oxidant hydrogen peroxide at 150 μM for 6 h and the protective effects of the compounds were evaluated. Among the sarains tested, sarain A was the most promising compound, improving mitochondrial function and decreasing reactive oxygen species levels in human neuroblastoma cells treated with the compound at 0.01, 0.1 and 1 μM. This compound was also able to increase the activity of the antioxidant enzymes superoxide dismutases by inducing the translocation of the nuclear factor E2-related factor 2 (Nrf2) to the nucleus at the lower concentrations tested (0.01 and 0.1 μM). Moreover, sarain A at 0.1 and 1 μM blocked the mitochondrial permeability transition pore (mPTP) opening through cyclophilin D inhibition. These results suggest that the protective effects produced by the treatment with sarain A are related with its ability to block the mPTP and to enhance the Nrf2 pathway, indicating that sarain A may be a candidate compound for further studies in neurodegenerative diseases.

Keywords

Sarains Oxidative stress Nrf2 mPTP Cyclophilin D Neuroprotection 

Notes

Acknowledgments

The research leading to these results has received funding from the following FEDER cofunded-grants. From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, AGL2014-58210-R, AGL2016-78728-R (AEI/FEDER, UE), ISCIII/PI16/01830 and RTC-2016-5507-2. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD and ITC-20161072. From the European Union’s Seventh Framework Programme managed by REA – Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Rebeca Alvariño
    • 1
  • Eva Alonso
    • 1
  • Marie-Aude Tribalat
    • 2
  • Sandra Gegunde
    • 1
  • Olivier P. Thomas
    • 2
    • 3
  • Luis M. Botana
    • 1
  1. 1.Departamento de Farmacología, Facultad de VeterinariaUniversidad de Santiago de CompostelaLugoSpain
  2. 2.Géoazur UMR Université Nice Sophia AntipolisNiceFrance
  3. 3.Marine Biodiscovery, School of ChemistryNational University of Ireland GalwayGalwayIreland

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