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Antioxidant and Protective Effects of Schinus terebinthifolius Raddi Against Doxorubicin-Induced Toxicity

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Abstract

Doxorubicin is an anticancer drug whose toxic effects on non-cancer cells are associated with increased oxidative stress. This study investigated the chemical composition, antioxidant activity of the methanolic extract of Schinus terebinthifolius Raddi leaves (MESL) as well as effects against doxorubicin-induced toxicity in human erythrocytes, K562 human erythroleukemia cells, and mouse hearts. The chemical composition indicated the presence of phenolic compounds, flavonoids, tannins, and ascorbic acid. MESL showed antioxidant activity by scavenging free radicals and inhibiting hemolysis and lipid peroxidation in human erythrocytes incubated with an oxidizing agent, and was able to increase the enzymatic activity of superoxide dismutase and glutathione peroxidase in human erythrocytes, without influencing the activity of enzyme catalase. The increase of oxidative hemolysis and malondialdehyde levels in erythrocytes incubated with doxorubicin was reduced by treatment with MESL. The cytotoxic activity of doxorubicin in erythroleukemia cells treated with MESL was unmodified. Additionally, the extract protected mice against the doxorubicin-induced cardiotoxicity. In conclusion, the MESL exhibits antioxidant activity, reducing doxorubicin-induced oxidative stress without changing the anticancer action of the drug, and protects against doxorubicin-induced cardiotoxicity. Hence, these findings suggest that these effects are via anti-oxidative by inhibiting free radicals, decreased oxidative stress, and increased antioxidant enzyme activity.

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Acknowledgements

This work was supported by grants from Foundation to Support to Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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  1. Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Federal University of Grande Dourados, Rodovia Dourados-Itahum, Km 12, Dourados, MS, 79804-970, Brazil

    Paola dos Santos da Rocha, Jaqueline Ferreira Campos, Ana Paula de Araújo Boleti, Edson Lucas dos Santos & Kely de Picoli Souza

  2. Federal University of Pernambuco, Av. Professor Moraes Rêgo, Recife, PE, 50670-901, Brazil

    Valéria Nunes-Souza

  3. Agricultural Sciences, Federal University of Grande Dourados, Rodovia Dourados-Itahum, Km 12, Dourados, Brazil

    Maria do Carmo Vieira

  4. Laboratório de Reatividade Cardiovascular, Federal University of Alagoas, Av. Lourival Melo Mota, Maceió, AL, 57072-900, Brazil

    Luiza Antas Rabelo

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  1. Paola dos Santos da Rocha
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Contributions

P.S.R., J.F.C., K.P.S., and E.L.S. conceived and designed the experiments; P.S.R., J.F.C., V.N.S., A.P.A.B., L.A.R., and K.P.S. performed the experiments; P.S.R., J.F.C., V.N.S., M.C.A., A.P.A.B., L.A.R., K.P.S., and E.L.S. analyzed the data; V.N.S., M.C.A., L.A.R., K.P.S., and E.L.S. contributed reagents/materials/analysis tools; P.S.R., J.F.C., L.A.R., K.P.S., and E.L.S. wrote the paper. All the authors have read and approved the final manuscript.

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Correspondence to Kely de Picoli Souza.

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Rocha, P.d.S.d., Campos, J.F., Nunes-Souza, V. et al. Antioxidant and Protective Effects of Schinus terebinthifolius Raddi Against Doxorubicin-Induced Toxicity. Appl Biochem Biotechnol 184, 869–884 (2018). https://doi.org/10.1007/s12010-017-2589-y

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