Modulation of the mTOR Pathway by Curcumin in the Heart of Septic Mice
Bruna A. C. Rattis,
Henrique L. Piva,
Andressa Duarte,
Frederico G. F. L. R. Gomes,
Janaína R. Lellis,
Danilo F. Soave,
Simone G. Ramos,
Antonio C. Tedesco,
Mara R. N. Celes
Affiliations
Bruna A. C. Rattis
Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-900, São Paulo, Brazil
Henrique L. Piva
Department of Chemistry, Faculty of Philosophy, Science and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-901, São Paulo, Brazil
Andressa Duarte
Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-900, São Paulo, Brazil
Frederico G. F. L. R. Gomes
Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-900, São Paulo, Brazil
Janaína R. Lellis
Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-900, São Paulo, Brazil
Danilo F. Soave
Department of Morphofunctional, Faculty of Medicine of Goianesia, University of Rio Verde, Goianesia 76380-000, Goias, Brazil
Simone G. Ramos
Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-900, São Paulo, Brazil
Antonio C. Tedesco
Department of Chemistry, Faculty of Philosophy, Science and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-901, São Paulo, Brazil
Mara R. N. Celes
Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-900, São Paulo, Brazil
mTOR is a signaling pathway involved in cell survival, cell stress response, and protein synthesis that may be a key point in sepsis-induced cardiac dysfunction. Curcumin has been reported in vitro as an mTOR inhibitor compound; however, there are no studies demonstrating this effect in experimental sepsis. Thus, this study aimed to evaluate the action of curcumin on the mTOR pathway in the heart of septic mice. Free curcumin (FC) and nanocurcumin (NC) were used, and samples were obtained at 24 and 120 h after sepsis. Histopathological and ultrastructural analysis showed that treatments with FC and NC reduced cardiac lesions caused by sepsis. Our main results demonstrated that curcumin reduced mTORC1 and Raptor mRNA at 24 and 120 h compared with the septic group; in contrast, mTORC2 mRNA increased at 24 h. Additionally, the total mTOR mRNA expression was reduced at 24 h compared with the septic group. Our results indicate that treatment with curcumin and nanocurcumin promoted a cardioprotective response that could be related to the modulation of the mTOR pathway.
