title: Atorvastatin reduces high glucose toxicity in rat peritoneal mesothelial cells.
abstract: 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.
authors.affiliation: NanoDrugs SL, Albacete, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Carrión
authors.forename: Francisco C
authors.initials: FC
authors.lastname: Pérez-Martínez
authors.forename: Silvia
authors.initials: S
authors.lastname: Monteagudo
authors.forename: María D
authors.initials: MD
authors.lastname: Pérez-Carrión
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez-Roldán
authors.forename: Valentín
authors.initials: V
authors.lastname: Ceña
authors.forename: Juan
authors.initials: J
authors.lastname: Pérez-Martínez
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D004847:Epithelial Cells / Q000187:drug effects*; D005947:Glucose / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D010537:Peritoneum / Q000166:cytology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D005947:Glucose