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Qualitative and quantitative comparison of the cytotoxic and apoptotic potential of phytosterol oxidation products with their corresponding cholesterol oxidation products

Published online by Cambridge University Press:  08 March 2007

Eileen Ryan ,
Jay Chopra ,
Florence McCarthy ,
Anita R. Maguire  and
Nora M. O'Brien
Eileen Ryan
Affiliation:
Department of Food and Nutritional Sciences, University College, Cork, Ireland
Jay Chopra
Affiliation:
Department of Chemistry, Analytical and Biological Chemistry Research Facility, University College, Cork, Ireland
Florence McCarthy
Affiliation:
Department of Chemistry, Analytical and Biological Chemistry Research Facility, University College, Cork, Ireland
Anita R. Maguire
Affiliation:
Department of Chemistry, Analytical and Biological Chemistry Research Facility, University College, Cork, Ireland
Nora M. O'Brien*
Affiliation:
Department of Food and Nutritional Sciences, University College, Cork, Ireland
*
*Corresponding author: Dr Nora M. O'Brien, fax +353 21 4270244, email [email protected]
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Abstract

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Phytosterols contain an unsaturated ring structure and therefore are susceptible to oxidation under certain conditions. Whilst the cytotoxicity of the analogous cholesterol oxidation products (COP) has been well documented, the biological effects of phytosterol oxidation products (POP)have not yet been fully ascertained. The objective of the present study was to examine the cytotoxicity of β-sitosterol oxides and their corresponding COP in a human monocytic cell line (U937), a colonic adenocarcinoma cell line (CaCo-2) and a hepatoma liver cell line (HepG2). 7β-Hydroxysitosterol, 7-ketositosterol, sitosterol-3β,5α,6β-triol and a sitosterol-5α,6α-epoxide–sitosterol-5β,6β-epoxide (6:1) mixture were found to be cytotoxic to all three cell lines employed; the mode of cell death was by apoptosis in the U937 cell line and necrosis in the CaCo-2 and HepG2 cells. 7β-Hydroxysitosterol was the only β-sitosterol oxide to cause depletion in glutathione, indicating that POP-induced apoptosis may not be dependent on the generation of an oxidative stress. A further objective of this study was to assess the ability of the antioxidants α-tocopherol, γ-tocopherol and β-carotene to modulate POP-induced cytotoxicity in U937 cells. Whilst α/γ-tocopherol protected against 7β-hydroxycholesterol-induced apoptosis, they did not confer protection against 7β-hydroxysitosterol-or 7-ketositosterol-induced toxicity, indicating that perhaps COP provoke different apoptotic pathways than POP. β-Carotene did not protect against COP- or POP-induced toxicity. In general, results indicate that POP have qualitatively similar toxic effects to COP. However, higher concentrations of POP are required to elicit comparable levels of toxicity.

Keywords

Phytosterol oxidesCholesterol oxidesCytotoxicityApoptosis
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 3 , September 2005 , pp. 443 - 451
Copyright
Copyright © The Nutrition Society 2005

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