Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse the inhibition of prostacyclin generation by aortas in streptozotocin diabetic rats.
The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and triglycerides compared to diabetic rats. The oxidative stress markers urinary isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma protein carbonyl content significantly increased in diabetic rats compared to nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly reduced oxidative stress levels compared to diabetic rats, but urinary isoprostane and liver TBARS remained significantly higher than nondiabetic rats. Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in diabetic rats compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not reverse that inhibition. These results were discussed in the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase and cyclooxygenase-2 activities and the genetic difference between rats and other mammals regarding the level of vascular superoxide dismutase (SOD) activity.
Mahfouz
M M
MM
University of Illinois, The H. E. Moore Heart Research Foundation Champaign, IL 61820, USA.
Kummerow
F A
FA
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D000069059:Atorvastatin; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D011464:Epoprostenol / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006538:Heptanoic Acids / Q000494:pharmacology*; D008055:Lipids / Q000097:blood*; D008297:Male; D018384:Oxidative Stress; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D013311:Streptozocin; D000069059:Atorvastatin; D011464:Epoprostenol