Antisenescent and antiinflammatory effect of N-acetylcysteine in peritoneal mesothelial cells

Abstract

Background

Peritoneal dialysis induces an intraperitoneal inflammatory reaction, which causes damage to the peritoneum. Inflammation also accelerates cellular senescence. We studied in vitro effect of the dialysates from peritoneal dialysis patients on the senescence of the peritoneal mesothelial cells (MCs). The effect of N-acetylcysteine (NAC) on that process was studied.

Methods

Replicative senescence was induced in MC cells exposed to culture medium, medium mixed with the dialysate ± NAC 0.025 mmol/L. After 10 passages, markers of the cellular senescence and secretory activity of the cells were measured. Additionally, the effect of NAC on the senescent cells was studied.

Results

Exposure of MC to the dialysate accelerated, more than in medium alone, their senescence as reflected by elongation of the population doubling time, increased expression of p21, p53 genes and β-galactosidase activity. Secretion of IL6 and transforming growth factor β (TGFβ) was increased, and fibrinolytic activity, as reflected by the tissue plasminogen activator/plasminogen activator inhibitor-1 ratio, was reduced. NAC slowed down the process of senescence in MC treated with the dialysate. NAC suppressed the proinflammatory properties of the senescent MC.

Conclusion

The proinflammatory properties of the peritoneal dialysate accelerate the senescence of MC. Decreased fibrinolytic activity of MC, increased secretion of IL6 and TGFβ may accelerate fibrosis of the peritoneum. Supplementation of NAC in patients treated with peritoneal dialysis may help preserve the peritoneum as the dialysis membrane.