Fluvastatin inhibits the expression of fibronectin in human peritoneal mesothelial cells induced by high-glucose peritoneal dialysis solution via SGK1 pathway
OBJECTIVE Continuous exposure of the peritoneal membrane to high glucose dialysis solutions can produce functional alterations in this membrane. We studied the toxic effects of high glucose (50 mmol/L and 83 mmol/L) and its reversal by atorvastatin (0.5 - 5 μmol/L) on cultures of rat peritoneal mesothelial cells (PMCs). METHODS Rat PMCs were harvested from the peritonea of male Sprague-Dawley rats and grown in M199 medium supplemented with 10% fetal bovine serum. The effects of high glucose (50 mmol/L and 83 mmol/L) on levels of reactive oxygen species (ROS), on caspase 3 activity, and on phospho-p38 mitogen-activated protein kinase (MAPK) in the cultures were evaluated. RESULTS Exposure to high glucose (for 4, 8, and 24 hours) increased intracellular levels of ROS and phospho-p38 MAPK (indices of cellular toxicity). Atorvastatin blocked these toxic effects of high glucose, being more effective against 50 mmol/L glucose (protective effects were observed above 0.5 μmol/L) than against 83 mmol/L (protective effects were observed above 2.5 μmol/L). Atorvastatin was also able to prevent glucose-induced increase in caspase 3 activity. CONCLUSIONS The present study shows that high glucose may promote oxidative stress and may activate apoptotic pathways in rat PMCs. These toxic effects could be reversed by atorvastatin.