Analysis of the cytotoxic, genotoxic, mutagenic, and pro-oxidant effect of synephrine, a component of thermogenic supplements, in human hepatic cells in vitro

Author(s)

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

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Sao Paulo, Inst Hlth & Soc, Dept Biosci, Rua Silva Jardim 136, BR-11015020 Santos, SP - Brazil

• Document type: Journal article
• Source: Toxicology; v. 422, p. 25-34, JUN 15 2019.
• Web of Science Citations: 0

Abstract

Thermogenic supplements containing synephrine (SN) are widely used to weight loss. SN is a proto-alkaloid naturally found in the bark of immature fruits of Citrus aurantium (bitter orange) that has been added to thermogenic supplements due to its chemical and pharmacological similarity with adrenergic amines, such as ephedrine and amphetamines. Although orally ingested SN is mainly metabolized in the liver, it remains unclear whether it affects the redox status and genetic material of human hepatic cells. The present study aims to examine whether SN affects cell viability, cell cycle, redox balance, genomic stability, and expression of the DNA damage response (DDR)-related genes ATM, ATR, CHEKI, CHECK2, TP53, and SIRTI in HepG2 cells used as in vitro hepatocyte model. SN induced overproduction of intracellular reactive oxygen species (ROS) after 6 h of treatment with the three concentrations tested (2, 20 and 200 mu M). After 24 h of treatment, SN at 200 mu M induced intracellular ROS overproduction and exerted cytostatic effects, while SN at 20 and 200 mu M increased the levels of GPx and GSH. SN was not cytotoxic (2-5000 mu M), genotoxic, and mutagenic and did not alter the expression of DDR-related genes (2-200 mu M), indicating that the fast/specific SN metabolization and upregulation of antioxidant defense components to detoxify intracellular ROS were sufficient to prevent intracellular damage in HepG2 cells. In conclusion, SN showed no cytotoxic, genotoxic, and mutagenic potential at relevant concentrations for thermogenic users in human hepatic cells in vitro, although, it plays pro-oxidative action, and cytostatic effects. Taken together, our results suggest that other investigations about the hazard absence of this thermogenic compound should be performed. (AU)

• FAPESP's process: 14/20344-9 - Mutagenicity, genotoxicity and changes in gene expression profile evaluation of synephrine dietary supplement in human cells in vitro
• Grantee: Diego Luis Ribeiro
• Support Opportunities: Scholarships in Brazil - Doctorate