Abstract
Tanshinone I (T-I, C18H12O3) is a diterpene found in Salvia miltiorrhiza Bunge (Danshen) and promotes cytoprotection in several experimental models. Chlorpyrifos (CPF) is an agrochemical that causes bioenergetics failure, redox impairment, inflammation, and cell death in animal tissues. Here, we investigated whether T-I would be able to prevent the consequences resulting from the exposure of the human dopaminergic SH-SY5Y cells to CPF. We found that a pretreatment with T-I at 2.5 µM for 2 h suppressed lipid peroxidation and protein carbonylation and nitration on the membranes of mitochondria extracted from the CPF-treated cells. Also, T-I reduced the production of radical superoxide (O2−•) by the mitochondria of the CPF-challenged cells. The production of nitric oxide (NO•) and hydrogen peroxide (H2O2) was also decreased by T-I in the cells exposed to CPF. The CPF-induced decrease in the activity of the complexes I-III, II-III, and V was abolished by a pretreatment with T-I. Loss of mitochondrial membrane potential (ΔΨm) and reduction in the production of adenosine triphosphate (ATP) were also prevented by T-I in the CPF-treated cells. T-I also induced anti-inflammatory effects in the CPF-treated cells by decreasing the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) and the activity of the nuclear factor-κB (NF-κB). Inhibition of heme oxygenase-1 (HO-1) or silencing of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) blocked the T-I-promoted mitochondrial protection and anti-inflammatory action. Overall, T-I depended on the Nrf2/HO-1 axis to prevent the deleterious effects caused by CPF in this experimental model.
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Funding
MRO receives a “Bolsa de Produtividade em Pesquisa 2—PQ2” fellow from the Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (CNPq) (protocol number 301273/2018–9). This work received financial support from CNPq (protocol number 400216/2016–7).
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Conceptualization: Marcos Roberto de Oliveira; methodology: Flávia Bittencourt Brasil, Fhelipe Jolner Souza de Almeida, Matheus Dargesso Luckachaki, Evandro Luiz Dall’Oglio, Marcos Roberto de Oliveira; formal analysis and investigation: Fhelipe Jolner Souza de Almeida, Matheus Dargesso Luckachaki, Marcos Roberto de Oliveira; writing — original draft preparation: Marcos Roberto de Oliveira; writing — review and editing: Flávia Bittencourt Brasil, Fhelipe Jolner Souza de Almeida, Matheus Dargesso Luckachaki, Evandro Luiz Dall’Oglio, Marcos Roberto de Oliveira; funding acquisition: Marcos Roberto de Oliveira and Evandro Luiz Dall’Oglio; Resources: Marcos Roberto de Oliveira and Evandro Luiz Dall’Oglio; Supervision: Marcos Roberto de Oliveira.
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Brasil, F.B., de Almeida, F.J.S., Luckachaki, M.D. et al. Suppression of Mitochondria-Related Bioenergetics Collapse and Redox Impairment by Tanshinone I, a Diterpenoid Found in Salvia miltiorrhiza Bunge (Danshen), in the Human Dopaminergic SH-SY5Y Cell Line Exposed to Chlorpyrifos. Neurotox Res 39, 1495–1510 (2021). https://doi.org/10.1007/s12640-021-00400-7
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DOI: https://doi.org/10.1007/s12640-021-00400-7