<i>In silico</i>, <i>in vitro,</i> and <i>in vivo</i> investigation of antioxidant potential and toxicity of ethyl ferulate
Creators: name: de Sá, Camila Bomfim
name: Lira, Andressa Brito
name: de Oliveira Filho, Abrahão Alves
name: de Oliveira, Kardilandia Mendes
name: da Paz, Alexandre Rolim
name: de Morais, Mayara Castro
name: de Sousa, Damião Pergentino
name: Dias, Gabriela Tafaela
name: Melo, Cinthia Rodrigues
name: de Luna Freire Pessôa, Hilzeth
name: Lima, Caliandra Maria Bezerra Luna
name: de Fátima Formiga Melo Diniz, Margareth
Publisher: name: Taylor & Francis
Year: 2021
Subjects: subject: Biochemistry
subject: Pharmacology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Ecology
subject: FOS: Biological sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: Science Policy

description: By submitting this manuscript, each author certifies that they have made a direct and substantial contribution to the work reported in the manuscript. In this manuscript the conception, design, investigation, acquisition of data and analysis, interpretation of data and writing of the article were conducted by author Camila Bomfim de Sá under the guidance of professors Margareth de Fátima Formiga Melo Diniz, Hilzeth de Luna Freire Pessôa and Caliandra Maria Bezerra Luna Lima, who also approved the final version of the manuscript. Professor Damião Pergentino de Sousa and his student Mayara Castro de Morais performed the production, synthesis and chemical characterization of ethyl ferulate (EF). Professor Abrahão Alves de Oliveira Filho assessed the <i>in silico</i> tests. PhD student Andressa Brito Lira participated in the critical review of the text for important intellectual content and assisted in the <i>in vitro</i> antioxidant activity and cytotoxicity tests. Kardilandia Mendes de Oliveira participated in acute oral toxicity tests evaluating the biochemical parameters. Students, Tafaela Dias and Cinthia Rodrigues Melo also assisted in the acute oral toxicity testing and preparing of slides for histopathological analysis. Pathologist Alexandre Rolim da Paz analyzed the histopathology results. EF, a phenolic compound of the large class of phenylpropanoids, is derived from ferulic acid and is produced both naturally and synthetically. Its principal pharmacological activities are: anti-inflammatory and antioxidant activity. This study aimed to investigate the <i>in silico</i>, <i>in vitro</i> and <i>in vivo</i> toxicity and antioxidant activity of EF. The <i>in silico</i> prediction showed more than 20 biological activities as well as good absorption at the biological membranes and no theoretical toxicity. However, EF presented high environmental toxicity. EF presented low hemolytic potential and exerted protective activity for the erythrocyte membrane for only blood type O. EF presented antioxidant activity against H<sub>2</sub>O<sub>2</sub> at all concentrations and all blood types, but no effect against phenylhydrazine, being unable to prevent its oxidative effects. In the acute nonclinical toxicological trial, the treated animals presented behavioral changes (e.g., sedation). Feed intake was higher for the 2000 mg/kg group, but with no significant difference in weight change. The biochemical parameters presented no differences between treated and control animals, and the organs remained intact with no change. Thus, EF presents a low toxic profile and this study provides important information about the toxicity of this compound, suggesting future safe use.