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01-10-2017 | ORIGINAL ARTICLE

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

Authors: Rebeca Alvariño, Eva Alonso, Marie-Aude Tribalat, Sandra Gegunde, Olivier P. Thomas, Luis M. Botana

Published in: Neurotoxicity Research | Issue 3/2017

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.

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Title: Evaluation of the Protective Effects of Sarains on H2O2-Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Neuroblastoma Cells
Authors: Rebeca Alvariño
Eva Alonso
Marie-Aude Tribalat
Sandra Gegunde
Olivier P. Thomas
Luis M. Botana
Publication date: 01-10-2017
Publisher: Springer US
Published in: Neurotoxicity Research / Issue 3/2017
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-017-9748-3

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

Abstract

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Abstract

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