OBJECTIVE: To investigate the modulation of superoxide dismutase, glutathione peroxidase, and catalase by cytokines and endotoxin in human peritoneal mesothelial cells. DESIGN: Cultured human peritoneal mesothelial cells were treated with various concentrations of interleukin-1 alpha, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, interleukin-8, transforming growth factor-beta (TGF beta), and lipopolysaccharide. Cell morphology was observed and the activities of superoxide dismutase, catalase, and glutathione peroxidase were assayed. The antioxidant enzyme activities of human peritoneal mesothelial cells were also compared with those of human liver and kidney tissues. RESULTS: Interleukin-1 alpha, TNF alpha, TGF beta, and lipopolysacharide caused dose-dependent cytotoxicities in mesothelial cells. The activities of these three antioxidant enzymes did not change after treatment with cytokines and endotoxin. The total superoxide dismutase activity of confluent human peritoneal mesothelial cells was found to be greater than that of human liver and kidney tissues and was composed mostly of manganese superoxide dismutase activity. Furthermore, glutathione peroxidase and catalase activities of human peritoneal mesothelial cells were lower than those of human liver and kidney tissues. CONCLUSION: In human peritoneal mesothelial cells, lack of induction of antioxidant enzymes by inflammatory cytokines, as well as high superoxide dismutase activity accompanied by insufficient glutathione peroxidase and catalase activities may both contribute to the susceptibility of these cells to oxidative damage. Therefore, appropriate management to decrease oxidative injury to the peritoneum should be taken into consideration when treating long-term continuous ambulatory peritoneal dialysis patients.

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