Neurochemical Research

, Volume 44, Issue 4, pp 884–896 | Cite as

Carvacrol Depends on Heme Oxygenase-1 (HO-1) to Exert Antioxidant, Anti-inflammatory, and Mitochondria-Related Protection in the Human Neuroblastoma SH-SY5Y Cells Line Exposed to Hydrogen Peroxide

  • Aline Lukasievicz Chenet
  • Adriane Ribeiro Duarte
  • Fhelipe Jolner Souza de Almeida
  • Cláudia Marlise Balbinotti Andrade
  • Marcos Roberto de OliveiraEmail author
Original Paper


The link between mitochondrial dysfunction, redox impairment, and inflammation leads to increased rates of brain cells loss in neurodegenerative diseases and in affective disorders. Carvacrol (CAR) is a component of essential oils found in Labiatae. CAR exerts antioxidant and anti-inflammatory effects in different cell types, as assessed in both in vitro and in vivo experimental designs. Nonetheless, it was not previously investigated whether and how CAR would prevent mitochondrial impairment in human cells exposed to a pro-oxidant challenge. Therefore, we analyzed here whether a pretreatment (for 4 h) with CAR (10–1000 µM) would promote mitochondrial protection in the human neuroblastoma cells SH-SY5Y exposed to hydrogen peroxide (H2O2). We found that CAR at 100 µM prevented the H2O2-induced decline in the activity of the complexes I and V, as well as on the levels of adenosine triphosphate (ATP). CAR also prevented the H2O2-elicited decrease in the activity of the mitochondrial enzymes aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. Moreover, CAR induced an antioxidant action by decreasing the levels of lipid peroxidation, protein carbonylation, and protein nitration in the mitochondrial membranes. Interestingly, CAR prevented the pro-inflammatory action of H2O2 by downregulating the transcription factor nuclear factor-κB (NF-κB). The inhibition of the heme oxygenase-1 (HO-1) enzyme by zinc protoporphyrin IX (ZnPP IX, 10 µM) suppressed the preventive effects caused by CAR regarding mitochondrial function and inflammation. Thus, it is suggested that CAR caused cytoprotective effects by an HO-1-dependent manner in SH-SY5Y cells exposed to H2O2.


Carvacrol Mitochondria Bioenergetics Antioxidant Anti-inflammatory HO-1 



This work was supported by the Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (CNPq; Edital Universal 2016; 400216/2016-7) and by the Fundação de Apoio à Pesquisa do Estado de Mato Grosso (FAPEMAT; Edital Universal; 222541/2015). ALC receives a CAPES fellow (Bolsa de Mestrado).

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

Supplementary material

11064_2019_2724_MOESM1_ESM.pdf (84 kb)
Fig. S1 The mitochondrial and nuclear fractions were checked in order to confirm that the samples do not contain cytoplasmic enzymes. (A) The activity of the cytoplasmic enzyme lactate dehydrogenase (LDH) was analyzed in the mitochondrial fraction obtained after isolation of the organelles. (B) The activity of the cytoplasmic enzyme lactate dehydrogenase (LDH) was analyzed in the nuclear fraction obtained after isolation of the cell nucleus. Supplementary material 1 (PDF 84 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Aline Lukasievicz Chenet
    • 1
    • 2
  • Adriane Ribeiro Duarte
    • 1
    • 2
  • Fhelipe Jolner Souza de Almeida
    • 1
    • 3
  • Cláudia Marlise Balbinotti Andrade
    • 1
    • 2
    • 3
  • Marcos Roberto de Oliveira
    • 1
    • 2
    • 3
    Email author
  1. 1.Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas BioativasUniversidade Federal de Mato Grosso (UFMT)CuiabaBrazil
  2. 2.Programa de Pós-Graduação em Química (PPGQ)Universidade Federal de Mato Grosso (UFMT)CuiabaBrazil
  3. 3.Programa de Pós-Graduação em Ciências da Saúde (PPGCS)Universidade Federal de Mato Grosso (UFMT)CuiabaBrazil

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