title: Evaluation of the cytotoxic effect of 7keto-stigmasterol and 7keto-cholesterol in human intestinal (Caco-2) cells.
abstract: The biological implications of cholesterol oxidation products have been investigated, though research on plant sterol oxidation products is scarce and in some cases contradictory. The cytotoxicity of 7keto(k)-stigmasterol versus 7keto(k)-cholesterol at different concentrations (0-120 μM) and incubation times (4-24h), in intestinal epithelial cells (Caco-2 cells) was evaluated. The 3-[4,5-dimethylthiazol-2-yl]-2,3-diphenyl tetrazolium bromide and neutral red uptake tests, mitochondrial membrane potential (ΔΨm), and relative DNA and RNA contents in the cell cycle phases were determined. Possible interaction effects between 7k-derivatives or non-oxidized stigmasterol were monitored. Endo/lysosomal activity was not impaired by either oxide. 7k-cholesterol showed a deleterious effect upon the mitochondrial compartment after 24h of exposure (120 μM), as well as upon ΔΨm when incubated at all concentrations (12/24h). Only cells incubated with 7k-cholesterol (120 μM) exhibited a decrease in RNA proportion in the G1 population. The presence of 7k-stigmasterol or stigmasterol with 7k-cholesterol reduced the deleterious metabolic effects upon mitochondrial functionality and integrity and the distribution of RNA contents in G1 and G2 phases. A decrease in the G1 phase proportion was detected in cells exposed to mixtures, without alterations in RNA content. The results obtained indicate the absence of 7k-stigmasterol cytotoxicity in Caco-2 cells and its capacity to reduce 7k-cholesterol toxicity.
authors: Department of Nutrition and Food Chemistry, Faculty of Pharmacy, University of Valencia, Avda, Vicente Andrés Estellés s/n, 46100 Burjassot, Spain.
authors: L
authors: L
authors: Alemany
authors: J M
authors: JM
authors: Laparra
authors: R
authors: R
authors: Barberá
authors: A
authors: A
authors: Alegría
mesh_terms: D018938:Caco-2 Cells; D002784:Cholesterol / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D013265:Stigmasterol / Q000633:toxicity*
chemical_list: D002784:Cholesterol; D013265:Stigmasterol