Dietary lipids, together with microflora, are now considered the main responsible in the pathogenesis of several chronic gastrointestinal disease. Oxysterols are cholesterol oxidation products derived exogenously from cholesterol during food processing or storage A defined mixture of the most common oxysterols found in cholesterol-rich foodstuffs was used in order to study its cytotoxic properties on intestinal cells. Differentiated CaCo-2 cells (D-CaCo-2) were chosen as a model of normal small intestine mucosa. In comparison with undifferentiated CaCo-2 cells (U-CaCo-2) D-CaCo-2 underwent apoptosis essentially due to the increase of intracellular reactive oxygen through the activation of NADPH oxidase complex. Indirect confirmation of these results comes from the significant apoptosis protection afforded by cell pretreatment with specific NADPH oxidase inhibitors or antioxidants. In conclusion, oxysterols are able to affect intestinal mucosa function through oxidative damage. The sensitivity of the cultures to oxysterols toxicity was highly affected by the CaCo-2 differentiation state suggesting an adaptation of CaCo-2 malignant cells to oxysterol oxidative insult compared to the corresponding differentiated phenotype.
Damaging effets of cholesterol oxidation products on intestinal epithelial cells
BIASI, Fiorella;POLI, Giuseppe;
2009-01-01
Abstract
Dietary lipids, together with microflora, are now considered the main responsible in the pathogenesis of several chronic gastrointestinal disease. Oxysterols are cholesterol oxidation products derived exogenously from cholesterol during food processing or storage A defined mixture of the most common oxysterols found in cholesterol-rich foodstuffs was used in order to study its cytotoxic properties on intestinal cells. Differentiated CaCo-2 cells (D-CaCo-2) were chosen as a model of normal small intestine mucosa. In comparison with undifferentiated CaCo-2 cells (U-CaCo-2) D-CaCo-2 underwent apoptosis essentially due to the increase of intracellular reactive oxygen through the activation of NADPH oxidase complex. Indirect confirmation of these results comes from the significant apoptosis protection afforded by cell pretreatment with specific NADPH oxidase inhibitors or antioxidants. In conclusion, oxysterols are able to affect intestinal mucosa function through oxidative damage. The sensitivity of the cultures to oxysterols toxicity was highly affected by the CaCo-2 differentiation state suggesting an adaptation of CaCo-2 malignant cells to oxysterol oxidative insult compared to the corresponding differentiated phenotype.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
