TY  - JOUR
  - O'Sullivan, A. J. and O'Callaghan, Y. C. and Woods, J. A. and O'Brien, N. M.
  - 2003
  - Journal of Applied Toxicology
  - Toxicity of cholesterol oxidation products to Caco-2 and HepG2 cells: Modulatory effects of alpha- and gamma-tocopherol
  - Validated
  - ()
  - 23
  - 3
  - 191
  - 197
  - 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 mum 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 mug 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% (IC50 value) was calculated. All four oxysterols investigated induced the greatest cytotoxic effects following 96 It 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 mum) of gamma-TOC were found to be more susceptible to oxysterol-induced toxicity under the conditions employed in this study. Copyright (C) 2003 John Wiley Sons, Ltd.
DA  - 2003/NaN
ER  - 

@article{V113214895,
   = {O'Sullivan, A. J. and O'Callaghan, Y. C. and Woods, J. A. and O'Brien, N. M.},
   = {2003},
   = {Journal of Applied Toxicology},
   = {Toxicity of cholesterol oxidation products to Caco-2 and HepG2 cells: Modulatory effects of alpha- and gamma-tocopherol},
   = {Validated},
   = {()},
   = {23},
   = {3},
  pages = {191--197},
   = {{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 mum 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 mug 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% (IC50 value) was calculated. All four oxysterols investigated induced the greatest cytotoxic effects following 96 It 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 mum) of gamma-TOC were found to be more susceptible to oxysterol-induced toxicity under the conditions employed in this study. Copyright (C) 2003 John Wiley Sons, Ltd.}},
  source = {IRIS}
}