Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis Effluent.

Recent studies have related mitochondrial impairment with peritoneal membrane damage during peritoneal dialysis (PD) therapy. Here, we assessed the involvement of mitochondrial dysfunction in the inflammatory response in human mesothelial cells, a hallmark in the pathogenesis of PD-related peritoneal membrane damage. Our ex vivo studies showed that IL-1ß causes a drop in the mitochondrial membrane potential in cells from peritoneal effluent. Moreover, when mitochondrial damage was induced by inhibitors of mitochondrial function, a low-grade inflammatory response was generated. Interestingly, mitochondrial damage sensitized mesothelial cells, causing a significant increase in the inflammatory response induced by cytokines, in which ROS generation and NF-κB activation appear to be involved, since inflammation was counteracted by both mitoTEMPO (mitochondrial ROS scavenger) and BAY-117085 (NF-κB inhibitor). Furthermore, the natural anti-inflammatory antioxidant resveratrol significantly attenuated the inflammatory response, by reversing the decline in mitochondrial membrane potential and decreasing the expression of IL-8, COX-2 and PGE2 caused by IL-1ß. These findings suggest that IL-1ß regulates mitochondrial function in mesothelial cells and that mitochondrial dysfunction could induce an inflammatory scenario that sensitizes these cells, causing significant amplification of the inflammatory response induced by cytokines. Resveratrol may represent a promising strategy in controlling the mesothelial inflammatory response to PD.

Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis.

Preservation of the peritoneal membrane is an essential determinant of the long-term outcome of peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) plays a central role in the pathogenesis of PD-related peritoneal membrane injury. We hypothesized that mitochondria may be implicated in the mechanisms that initiate and sustain peritoneal membrane damage in this setting. Hence, we carried out ex vivo studies of effluent-derived human mesothelial cells, which disclosed a significant increase in mitochondrial reactive oxygen species (mtROS) production and a loss of mitochondrial membrane potential in mesothelial cells with a fibroblast phenotype, compared to those preserving an epithelial morphology. In addition, in vitro studies of omentum-derived mesothelial cells identified mtROS as mediators of the EMT process as mitoTEMPO, a selective mtROS scavenger, reduced fibronectin protein expression induced by TGF-ß1. Moreover, we quantified mitochondrial DNA (mtDNA) levels in the supernatant of effluent PD solutions, disclosing a direct correlation with small solute transport characteristics (as estimated from the ratio dialysate/plasma of creatinine at 240 min), and an inverse correlation with peritoneal ultrafiltration. These results suggest that mitochondria are involved in the EMT that human peritoneal mesothelial cells suffer in the course of PD therapy. The level of mtDNA in the effluent dialysate of PD patients could perform as a biomarker of PD-induced damage to the peritoneal membrane.

Actuación de enfermería ante un paciente con infección aguda por el virus de la hepatitis C en hemodiálisis en tratamiento con antivirales de acción directa / No disponible

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