Synephrine and caffeine combination promotes cytotoxicity, DNA damage and transcriptional modulation of apoptosis-related genes in human HepG2 cells

Autor(es)

Leao, Taina Keiller ^[1] ; Ribeiro, Diego Luis ^[2] ; Thomazela Machado, Ana Rita ^[1] ; Costa, Tassia Rafaela ^[1] ; Sampaio, Suely Vilela ^[1] ; Greggi Antunes, Lusania Maria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS; v. 868, AUG-SEP 2021.
• Citações Web of Science: 0

Resumo

The abusive consumption of thermogenic supplements occurs worldwide and deserves special attention due to their use to stimulate weight loss and prevent obesity. Thermogenic formulations usually contain Synephrine (SN) and Caffeine (CAF), stimulating compounds extracted from natural sources, but no genetic toxicology studies have predicted this hazardous combination potential. This study examined the toxicogenomic responses induced by SN and CAF, either alone or in combination, in the human hepatic cell line HepG2 in vitro. SN (0.03-30 mu M) and CAF (0.6-600 mu M) alone did neither decrease cell viability nor induce DNA damage, as assessed using the MTT and comet assays, respectively. SN (3 mu M) and CAF (30-600 mu M) were combined at concentrations similar to those found in commercial dietary supplements. SN/CAF at 3:90 and 3:600 mu M ratios significantly decreased cell viability and increased DNA damage levels in HepG2 cells. CAF (600 mu M) and the SN/ CAF association at 3:60, 3:90, and 3:600 mu M ratios promoted cell death by apoptosis, as demonstrated by flow cytometry. Similar results were observed in gene expression (RT-qPCR): SN/CAF up-regulated the expression of apoptosis-(BCL-2 and CASP9) and DNA repair-related (XPC) genes. SN/CAF at 3:90 mu M also downregulated the expression of cell cycle control (CDKN1A) genes. In conclusion, the SN/CAF combination reduces cell viability by inducing apoptosis, damages DNA, and modulates the transcriptional expression of apoptosis-, cell cycle-, and DNA repair-related genes in human hepatic (HepG2) cells in vitro. These effects can be worrisome to consumers of thermogenic supplements. (AU)

• Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
• Beneficiário: Suely Vilela
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/00740-0 - Avaliação do potencial terapêutico de L-aminoácido oxidases isoladas de peçonhas de serpentes como antitumoral: estudos de genotoxicidade e expressão gênica
• Beneficiário: Tássia Rafaella Costa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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