ATORVASTATIN REDUCES HIGH GLUCOSE TOXICITY IN RAT PERITONEAL MESOTHELIAL CELLS

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 mu mol/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 mu mol/L) than against 83 mmol/L (protective effects were observed above 2.5 mu mol/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.