Impact of natural antioxidants on oxidative stress in Caco-2 human colon cells.

摘要

Reactive oxygen species, free radicals, and oxidative products, such as lipid hydroperoxides, have been associated with many degenerative diseases in the gastrointestinal system of humans. Studies were conducted using Caco-2 human colon carcinoma cells, to evaluate cellular damage and antioxidant enzyme responses caused by exposing cells to hydrogen peroxide (H2O 2) and a dietary oxidant, oleic acid hydroperoxide (OAHPx). This study showed that with increasing H2O2 and OAHPx concentrations, cell membrane leakage, cell lipid peroxidation, and DNA damage increased, whereas the three antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase responded differently, as shown by the developed mathematical models. The existing cellular antioxidant mechanisms were not capable of completely detoxifying 100-250 muM hydrogen peroxide and 5-25 muM OAHPx, indicating that exogenous dietary antioxidants are necessary to reduce oxidative stress in the human gastrointestinal tract. Therefore, the effects of 24 h supplementation of Caco-2 cells with four antioxidants, genistein (25, 50, 100 muM), daidzein (25, 50 muM), carnosic acid (25, 50, 100 muM), and carnosol (25, 50, 100 muM), against the oxidative stress mediated by 5 muM OAHPx, the dietary oxidant, were investigated.; Once Caco-2 cell cultures were oxidatively stressed, cell cultures supplemented with the four antioxidants, genistein, daidzein, carnosic acid and carnosol significantly reduced cell injury induced by OAHPx compared to non-supplemented oxidatively stressed cultures. However, cytotoxicity mediated by 5 muM OAHPx was not completely prevented by these antioxidant compounds at tested concentrations. All four antioxidant compounds affected antioxidant enzyme activities after 24 h incubation with Caco-2 cells depending on their supplemented concentrations. Based upon the results of this study, it could be suggested that detoxification of OAHPx by these four antioxidants can be partly due to each compound's ability to increase or maintain antioxidant enzyme activity at basal levels. All four antioxidants significantly lowered DNA damage induced by OAHPx indicating their cancer-preventing effects in humans.