Type

Journal Article

Authors

N M O'Brien
J A Woods
Y C O'Callaghan
A J O'Sullivan

Subjects

Pharmacology

Topics
drug effects cholesterol analogs derivatives cell survival antioxidants caco 2 cells humans pharmacology time factors hydroxycholesterols neutral red inhibitory concentration 50 cholesterol alpha oxide toxicity alpha tocopherol gamma tocopherol

Toxicity of cholesterol oxidation products to Caco-2 and HepG2 cells: modulatory effects of alpha- and gamma-tocopherol. (2003)

Abstract Cholesterol can be oxidized to form a variety of cholesterol oxidation products also known as oxysterols. The aims of the present study were to compare the cytotoxic effects of four oxysterols, namely 25-hydroxycholesterol (25-OHC), 7beta-hydroxycholesterol (7beta-OHC), cholesterol-5beta,6beta-epoxide (beta-epox) and cholesterol-5alpha,6alpha-epoxide (alpha-epox), in two human cell culture models. Further, the ability of 10 and 100 micro m alpha- and gamma-tocopherol (alpha-TOC and gamma-TOC, respectively) to protect against oxysterol-induced cytotoxicity was also assessed. Human colonic adenocarcinoma Caco-2 and human hepatoma HepG2 cells were supplemented with increasing concentrations of 25-OHC, 7beta-OHC, beta-epox and alpha-epox (0-25 micro g ml(-1)) for 24, 48 or 96 h. Following 24-h and 48-h exposure, test media were replaced with normal growth media and the cells were maintained for 72 and 48 h, respectively. The 96-h exposure represented a constant challenge to the cells. Cytotoxicity was assessed using the neutral red uptake assay. The concentration of compound that inhibited cell viability by 50% (ic(50) value) was calculated. All four oxysterols investigated induced the greatest cytotoxic effects following 96 h of exposure. 25-Hydroxycholesterol exhibited the greatest cytotoxicity in both cell lines. Both beta-epox and alpha-epox were more toxic to HepG2 cells than to Caco-2 cells after the 48-h exposure. Pretreatment of cells with either alpha- or gamma-TOC did not protect against oxysterol-induced cytotoxicity. The caco-2 cells treated with the high concentration (100 micro m) of gamma-TOC were found to be more susceptible to oxysterol-induced toxicity under the conditions employed in this study.
Collections Ireland -> University College Cork -> PubMed

Full list of authors on original publication

N M O'Brien, J A Woods, Y C O'Callaghan, A J O'Sullivan

Experts in our system

1
Nora M O'Brien
University College Cork
Total Publications: 98
 
2
Yvonne C O'Callaghan
University College Cork
Total Publications: 38
 
3
Aifric O'Sullivan
University College Dublin
Total Publications: 11