Marketable 1,3-dimethylamylamine and caffeine-based thermogenic supplements: Regulatory genotoxicity assessment through in vitro and in silico approaches.

Autor: Carrão Dantas EK; Laboratory of Environmental Mutagenicity, Department of Biophysics and Biometry, Rio de Janeiro State University, Rio de Janeiro, Brazil., Ferreira CLS; Laboratory of Environmental Mutagenicity, Department of Biophysics and Biometry, Rio de Janeiro State University, Rio de Janeiro, Brazil., da Cunha Goldstein A; Laboratory of Environmental Mutagenicity, Department of Biophysics and Biometry, Rio de Janeiro State University, Rio de Janeiro, Brazil., da Silva Fernandes A; Laboratory of Environmental Mutagenicity, Department of Biophysics and Biometry, Rio de Janeiro State University, Rio de Janeiro, Brazil., Anastacio Ferraz ER; Faculty of Pharmacy, Fluminense Federal University, Niteroi, Brazil., Felzenszwalb I; Laboratory of Environmental Mutagenicity, Department of Biophysics and Biometry, Rio de Janeiro State University, Rio de Janeiro, Brazil., Araújo-Lima CF; Laboratory of Environmental Mutagenicity, Department of Biophysics and Biometry, Rio de Janeiro State University, Rio de Janeiro, Brazil.; Department of Genetics and Molecular Biology, Federal University of Rio de Janeiro State, Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Journal of toxicology and environmental health. Part A [J Toxicol Environ Health A] 2024 Mar 18; Vol. 87 (6), pp. 245-265. Date of Electronic Publication: 2024 Jan 10.
DOI: 10.1080/15287394.2023.2294925
Abstrakt: The consumption of dietary supplements to enhance physical performance has increased significantly in the last century, especially thermogenic pre-workout supplements. Nevertheless, this industry has faced criticism for inadequate safety measures surveillance in regulatory issues regarding their products. The aims of our study were to investigate two pre-workout supplements with respect to (1) mutagenicity utilizing Salmonella /microsome assay; (2) genotoxicity employing cytokinesis-block micronucleus (CBMN) assay protocols; and (3) hepatocytoxicity using WST cell proliferation, activities of lactate dehydrogenase (LDH) and alkaline phosphatase using human liver carcinoma (HepG2) and mouse fibroblast (F C3H) cells. Oxidative stress was determined through glutathione (GSH) measurement and in silico for predictions of pharmacokinetics and toxicity for the most abundant isolated substances present in these supplements. Both supplements induced mutagenicity in all examined bacterial strains, especially in the presence of exogenous metabolism. Further, tested supplements significantly elevated the formation of micronuclei (MN) as well as other cellular phenomena. Concentration- and time-dependent curves were observed for hepatotoxicity in both studied cell lines. In addition, both supplements decreased levels of intracellular and extracellular GSH. In silico predictions showed that the isolated individual compounds failed to induce the observed outcomes. Our findings provide contributions to the molecular mechanisms underlying two pre-workout supplement-induced toxicity and the need for surveillance.
Databáze: MEDLINE