Abstract
Carnosic acid (CA; C20H28O4) is a phenolic diterpene found in rosemary (Rosmarinus officinalis L.) and exhibits protective properties, e.g., antioxidant, anti-inflammatory, antitumor, and antimicrobial activities. In this context, CA has been viewed as a neuroprotective agent due to its ability in rescuing neuronal cells from pro-oxidant and pro-apoptotic challenges. In the present work, we found that CA pretreatment at 1 µM for 12 h suppressed the mitochondria-related pro-oxidant and mitochondria-dependent pro-apoptotic effects of chlorpyrifos (CPF) in human neuroblastoma SH-SY5Y cells. CA prevented mitochondrial membrane potential disruption and decreased the levels of oxidative stress markers in mitochondrial membranes obtained from cells exposed to CPF. CA also inhibited cytochrome c release and activation of the caspases-9 and -3, as well as decreased DNA fragmentation, in CPF-treated cells. CA upregulated the content of glutathione (GSH) in mitochondria by a mechanism involving the activation of the phosphoinositide-3-kinase (PI3K)/Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, since inhibition of PI3K/Akt or silencing of Nrf2 using siRNA strategy abolished the protection exerted by CA in SH-SY5Y cells. Therefore, CA protected mitochondria of SH-SY5Y cells through the activation of the PI3K/Akt/Nrf2 axis, causing upregulation of the mitochondrial GSH content and consequent antioxidant and anti-apoptotic effects.
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This work was supported by CNPq. GCF is supported by Edital APQ1/FAPERJ.
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12640_2016_9620_MOESM1_ESM.pdf
The effects of a pretreatment with carnosic acid (CA) at 0.1–2 μM for 12 h on the viability of SH-SY5Y cells exposed to chlorpyrifos (CPF) for 24 h. Data are presented as the mean ± SD of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, *p < 0.05 versus the control group, a different from CPF-treated cells. Supplementary material 1 (PDF 96 kb)
12640_2016_9620_MOESM2_ESM.pdf
The effects of Nrf2 siRNA (48 h) on nuclear Nrf2 content in SH-SY5Y cells exposed to carnosic acid (CA). Data are presented as the mean ± SD of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, *p < 0.05 versus the control group, a p < 0.05 versus carnosic acid-treated cells transfected with negative control (NC) siRNA. Supplementary material 2 (PDF 97 kb)
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de Oliveira, M.R., Peres, A., Ferreira, G.C. et al. Carnosic Acid Affords Mitochondrial Protection in Chlorpyrifos-Treated Sh-Sy5y Cells. Neurotox Res 30, 367–379 (2016). https://doi.org/10.1007/s12640-016-9620-x
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DOI: https://doi.org/10.1007/s12640-016-9620-x