Objectives: 

Disturbances in redox equilibrium can lead to a pro-inflammatory state, and chronic gut inflammation has been demonstrated to be associated with enhanced production of reactive oxygen species. Several mechanisms involved in intestinal inflammation, such as Toll-like receptors (TLRs) stimulation and the increase in 5-HT extracellular availability have also been shown to be involved in intracellular redox stress. However, the oxidative damage in intestinal epithelial cells yielded by either inflammatory factors or TLRs activation remains unknown. The aim of the present work has been to determine the contribution of the activation of TLR3 and TLR4, and the inflammatory factors adenosine, melatonin and 5-HT to the oxidative stress in human enterocyte-like Caco-2 cells.

Materials: 

The oxidative stress was determined by measuring the levels of lipid peroxidation (MDA + 4-HDA) and protein carbonyls, and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx).

Results: 

Activation of TLR3 and TLR4 by poly(I:C)and LPS respectively, and treatment of the cells with high concentration of adenosine, melatonin or 5-HT, have shown to increase the oxidative damage of lipids and proteins in these cells. In addition, the activity of catalase was reduced by poly(I:C), adenosine and 5-HT; the activity of SOD, was inhibited by LPS, poly(I:C), adenosine, melatonin and 5-HT; and the activity of GPx was inhibited by LPS.

Conclusions: 

These results demonstrate that the activation of TLR3 and 4, and adenosine, melatonin and 5-HT treatments contribute to the inhibition of antioxidant enzymes activity and cause oxidative stress in intestinal epithelial cells.