title: Phytosterol supplementation reduces metabolic activity and slows cell growth in cultured rat cardiomyocytes.
abstract: Besides being cholesterol-lowering agents, phytosterols (PS) can inhibit the growth and development of tumours. The anti-neoplastic activity is accounted for by PS incorporation into cell membranes, resulting in the interference of membrane functionality. The similarity between the PS cholesterol-lowering and anti-neoplastic effective doses deserves attention on the possible adverse effects even in non-neoplastic cells. To date, few studies have addressed the clarification of this important issue. In the present study, we supplemented primary, non-neoplastic neonatal rat cardiomyocytes with two different PS concentrations (3 or 6 μg/ml), both within the range of human plasma concentration. Cardiac cells were chosen as an experimental model since the heart has been reported as the target organ for subchronic toxicity of PS. Following supplementation, a dose-dependent incorporation of PS and a decrease in cholesterol content were clearly evidenced. PS did not induce apoptosis but caused a reduction in metabolic activity (measured as 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) conversion) and a slowing down of cell growth. The lower MTT conversion and the similar lactate dehydrogenase release could suggest that PS more efficiently target mitochondria than plasma membrane integrity. The replacement of cholesterol by PS could also have caused the observed slowing down of cell growth and the reduction in metabolic activity, which could rely on the PS increase, cholesterol decrease, or both. The present study is the first report on the effect of PS in cardiac cells, and although it is difficult to translate the obtained results to the health of heart tissue, it raises concerns about the safety of long-term exposure to physiologically relevant PS concentrations.
authors.affiliation: Department of Food Sciences, Campus di Scienze degli Alimenti, Università di Bologna, Cesena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Danesi
authors.forename: Federico
authors.initials: F
authors.lastname: Ferioli
authors.forename: Maria Fiorenza
authors.initials: MF
authors.lastname: Caboni
authors.forename: Elisa
authors.initials: E
authors.lastname: Boschetti
authors.forename: Mattia
authors.initials: M
authors.lastname: Di Nunzio
authors.forename: Vito
authors.initials: V
authors.lastname: Verardo
authors.forename: Veronica
authors.initials: V
authors.lastname: Valli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bordoni
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009994:Osmolar Concentration; D010840:Phytosterols / Q000009:adverse effects / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010840:Phytosterols; D002784:Cholesterol