p-synephrine induces transcriptional changes via the cAMP/PKA pathway but not cytotoxicity or mutagenicity in human gastrointestinal cells

Autor(es)

Ribeiro, Diego Luis ^[1] ; Thomazela Machado, Ana Rita ^[2] ; Machado, Carla ^[1] ; Aissa, Alexandre Ferro ^[2] ; Dos Santos, Patrick Wellington ^[2] ; Mazzaron Barcelos, Gustavo Rafael ^[3] ; Greggi Antunes, Lusania Maria ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto - Brazil

^[3] Univ Fed Sao Paulo, Inst Hlth & Soc, Dept Biosci, BR-11015020 Santos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES; v. 84, n. 5 DEC 2020.
• Citações Web of Science: 0

Resumo

p-Synephrine (SN) is an alkaloid added to thermogenic formulations for weight loss that is predominantly absorbed in the human gastrointestinal tract (GI). As the adverse effects of SN on GI cells remain unclear, the aim of present study was to examine whether SN affected cell viability, cell cycle kinetics, genomic stability, redox status, and expression of cAMP/PKA pathway genes related to metabolism/energy homeostasis in stomach mucosa (MNP01) and colon adenocarcinoma (Caco-2) human cells. p-Synephrine at 25-5000 mu M was not cytotoxic to both cell lines. At 2-200 mu M, SN increased the formation of reactive oxygen species (ROS) but also enhanced levels of antioxidant defense molecules glutathione (GSH) and catalase (CAT) activity, which may account for the absence of cytotoxicity/mutagenicity in both cell lines. SN induced expression of the cAMP/PKA pathway genes ADCY3 and MAPK1 in MNP01 cells and MAPK1, GNAS, PRKACA, and PRKAR2A in Caco-2 cells, as well as modulated the transcription of genes related to cell proliferation (JUN; AKT1) and inflammation (RELA; TNF) in both cell lines. Therefore, the improved antioxidant state mitigated pro-oxidative effects attributed to SN. Evidence indicates that SN does not appear to exhibit adverse potential but modulated the cAMP/PKA pathway in human GI cell lines. (AU)

• Processo FAPESP: 14/20344-9 - Avaliação da mutagenicidade, genotoxicidade e alterações no perfil de expressão gênica induzida pelo suplemento alimentar sinefrina em células humanas in vitro
• Beneficiário: Diego Luis Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Doutorado