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Mutagenicity, genotoxicity and changes in gene expression profile evaluation of synephrine dietary supplement in human cells in vitro

Grant number: 14/20344-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2015
Effective date (End): October 31, 2017
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Lusânia Maria Greggi Antunes
Grantee:Diego Luis Ribeiro
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Previously used for the treatment of hypotension as well as ocular decongestant, synephrine is a proto-alkaloid that is naturally found in the immature fruit orpeelof Citrus aurantium (bitter orange) and widely used in dietary supplements aimed weight loss and improvement sports performance. Studies about clinical effects of synephrine as hypertension and tachycardia have been described for humans and animals, but genetic toxicology studies are still missing in the literature. The aim of this study is evaluate the genotoxicity and mutagenicity of synephrine as well as analyze possible changes in enzyme parameters and also determine the effects on gene expression of human cell lines in vitro, and thus obtain data on toxicogenetics effects of this substance. To this end, will be employed human hepatic tumor line (HepG2), colorectal tumor line (Caco-2) and normal gastric primary line. To obtain data on the possible cytotoxic, genotoxic and mutagenic action of synephrine internationally validated tests such as MTT, comet and cytome micronucleus will be used; evaluated the effects on the cellular redox state by different enzymatic measurements and changes in the expression of genes related to oxidative stress, antioxidant defense, cell cycle and DNA repair, to obtain data that can elucidate the interactions and possible adverse effects of this substance used as a dietary supplement. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RIBEIRO, DIEGO LUIS; THOMAZELA MACHADO, ANA RITA; MACHADO, CARLA; AISSA, ALEXANDRE FERRO; DOS SANTOS, PATRICK WELLINGTON; MAZZARON BARCELOS, GUSTAVO RAFAEL; GREGGI ANTUNES, LUSANIA MARIA. p-synephrine induces transcriptional changes via the cAMP/PKA pathway but not cytotoxicity or mutagenicity in human gastrointestinal cells. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 84, n. 5 DEC 2020. Web of Science Citations: 0.
RIBEIRO, DIEGO LUIS; THOMAZELA MACHADO, ANA RITA; MACHADO, CARLA DA SILVA; DA SILVA SANTOS, PATRICK WELLINGTON; AISSA, ALEXANDRE FERRO; MAZZARON BARCELOS, GUSTAVO RAFAEL; GREGGI ANTUNES, LUSANIA MARIA. Analysis of the cytotoxic, genotoxic, mutagenic, and pro-oxidant effect of synephrine, a component of thermogenic supplements, in human hepatic cells in vitro. Toxicology, v. 422, p. 25-34, JUN 15 2019. Web of Science Citations: 0.

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