N-acetylcysteine prevents mitochondria from oxidative injury induced by conventional peritoneal dialysate in human peritoneal mesothelial cells.
BACKGROUND
Bioincompatible peritoneal dialysate fluids (PDFs) may lead to peritoneal injury. The present study investigated the possible effects of N-acetylcysteine (NAC) during conventional PDF exposure for human peritoneal mesothelial cells (HPMCs).


METHODS
Cultured HPMCs were incubated with conventional 1.5% dextrose PDF for different time periods, and NAC was utilized as the antioxidant. The cell survival, superoxide accumulation, mitochondrial membrane potential (Deltapsim), expression of heat shock protein 72(HSP72), catalase, superoxide dismutase (SOD), and glutathione content of HPMCs were evaluated.


RESULTS
HPMC exposed to PDF resulted in a significant decrease in cell survival in a time-dependent manner, which was reversed by NAC. PDF exposure resulted in intracellular accumulation of superoxide in a time-dependent manner, with collapse of Deltapsim as well. The activity of enzymatic antioxidant, SOD and catalase remained the same in all groups. However, the reduced glutathione was significantly suppressed after PDF exposure. NAC treatment preserved the content of intracellular reduced glutathione, and also attenuated the PDF-induced superoxide accumulation and Deltapsim collapse. Moreover, the enhanced expression of HSP72 induced by PDF exposure was also reversed by NAC.


CONCLUSIONS
Depletion of a nonenzymatic antioxidant, i.e. reduced glutathione, in HPMC is a crucial cause of PDF-induced oxidative stress. NAC protects HPMCs from PDF-induced cellular damage by preserving the reduced glutathione.
Kuo
Hung-Tien
HT
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lee
Jia-Jung
JJ
Hsiao
Hui-Hsu
HH
Chen
Hsiang-Wen
HW
Chen
Hung-Chun
HC
D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000494:pharmacology*; D004848:Epithelium; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress; D010537:Peritoneum / Q000166:cytology*
D015314:Dialysis Solutions; D000111:Acetylcysteine