Abstract
Chronic kidney disease (CKD) is characterized by an oxidative stress status, driving some CKD-associated complications, even at the gastrointestinal level. Indoxyl Sulfate (IS) is a protein-bound uremic toxin, poorly eliminated by dialysis. This toxin is able to affect the intestinal system, but its molecular mechanism/s in intestinal epithelial cells (IECs) remain poorly understood. This study’s aim was to evaluate the effect of IS (31.2–250 µM) on oxidative stress in IEC-6 cells and on the intactness of IECs monolayers. Our results indicated that IS enhanced oxidative cell damage by inducing reactive oxygen species (ROS) release, reducing the antioxidant response and affecting Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation as well its related antioxidant enzymes. In the wound healing assay model, IS reduced IEC-6 migration, slightly impaired actin cytoskeleton rearrangement; this effect was associated with connexin 43 alteration. Moreover, we reported the effect of CKD patients’ sera in IEC-6 cells. Our results indicated that patient sera induced ROS release in IEC-6 cells directly related to IS sera content and this effect was reduced by AST-120 serum treatment. Results highlighted the effect of IS in inducing oxidative stress in IECs and in impairing the intactness of the IECs cell monolayer, thus significantly contributing to CKD-associated intestinal alterations.
Highlights
Chronic kidney disease (CKD) progression induces multiple organs dysfunctions with various clinical aspects contributing to uremic syndrome
To investigate the effect of indoxyl sulfate (IS) on oxidative stress in intestinal epithelial cells (IECs)-6 cells, we evaluated intracellular reactive oxygen species (ROS) release
Our results showed that IS significantly increased ROS production in IEC-6 cells (31.2–250 μM; p < 0.05 vs. control; Figure 1)
Summary
Chronic kidney disease (CKD) progression induces multiple organs dysfunctions with various clinical aspects contributing to uremic syndrome. CKD is ascribed to the progressive retention of a large number of compounds that are excreted by healthy kidneys. These retained compounds are called uremic toxins because of their damaging effects on various physiological functions in CKD patients [1,2]. The accumulation of uremic toxins, such as indoxyl sulfate (IS), seems to be involved in the progression of renal failure and in its associated complications. It has been reported that IS increases inflammation and oxidative stress in macrophages and, more recently, in central nervous system cells, contributing to immune dysfunctions and neurodegenerative complications often observed in these patients [8,9,10]
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