title: Major components of energy drinks (caffeine, taurine, and guarana) exert cytotoxic effects on human neuronal SH-SY5Y cells by decreasing reactive oxygen species production.
abstract: METHODS
  To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs).
  
  
  RESULTS
  On human neuronal SH-SY5Y cells, caffeine (0.125-2 mg/mL), taurine (1-16 mg/mL), and guarana (3.125-50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5-50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis.
  
  
  CONCLUSIONS
  Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or "antioxidative stress"), could be a cause of in vitro toxicity induced by these drugs.
authors.affiliation: Department of Biochemistry, Center of Oxidative Stress Research, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. fzchulia.biomed@gmail.com
authors.forename: Fares
authors.initials: F
authors.lastname: Zeidán-Chuliá
authors.forename: Daniel Pens
authors.initials: DP
authors.lastname: Gelain
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Kolling
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Rybarczyk-Filho
authors.forename: Priscilla
authors.initials: P
authors.lastname: Ambrosi
authors.forename: Silvia Resende
authors.initials: SR
authors.lastname: Terra
authors.forename: André Simões
authors.initials: AS
authors.lastname: Pires
authors.forename: João Batista Teixeira
authors.initials: JB
authors.lastname: da Rocha
authors.forename: Guilherme Antônio
authors.initials: GA
authors.lastname: Behr
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D061215:Energy Drinks; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008954:Models, Biological; D009410:Nerve Degeneration / Q000473:pathology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D032126:Paullinia / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D013654:Taurine; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D002110:Caffeine; D002374:Catalase; D013482:Superoxide Dismutase