Statins ameliorate glomerular permeability changes in streptozotocin-induced diabetic rats.
OBJECTIVE
Statins reduce albumin excretion rate and retard the progression of diabetic nephropathy. Whether statins alter size selectivity of glomerular filtration in diabetic rats is not known.


METHODS
The creatinine clearance and the permeability of glomeruli to a group of fluorescein isothiocyanate dextrans of varying molecular weights were studied in rats with streptozotocin-induced diabetes that were treated with either 10 mg/kg rosuvastatin or simvastatin for 5 weeks.


RESULTS
Statin therapy did not significantly alter the increased creatinine clearance in diabetic rats. During the 5 hours of urine collection there was near-complete filtration of 4-, 10-, and 20-kD dextrans in all rat groups studied. The filtration of 70- and 40-kD dextrans was significantly increased in diabetic rats after 5 weeks of diabetes. Rosuvastatin but not simvastatin was associated with partial normalization of glomerular filtration of the 70- and 40-kD dextrans. Treatment with mevalonate (150 mg/kg in drinking water for 5 weeks) reversed the favorable effects of rosuvastatin on glomerular permeability.


CONCLUSIONS
Statin treatment of rats with streptozotocin-induced diabetes ameliorates glomerular permeability changes. The favorable effect of rosuvastatin is probably related to the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, because mevalonate treatment reversed the favorable effects of rosuvastatin.
Mooradian
Arshag D
AD
Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, Missouri, USA. arshag.mooradian@jax.ufl.edu
Haas
Michael J
MJ
D000818:Animals; D003404:Creatinine / Q000378:metabolism; D003911:Dextrans / Q000493:pharmacokinetics; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005456:Fluorescent Dyes; D005464:Fluorobenzenes / Q000494:pharmacology*; D005919:Glomerular Filtration Rate; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008798:Mevalonic Acid / Q000494:pharmacology; D008970:Molecular Weight; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000494:pharmacology*; D013311:Streptozocin; D013449:Sulfonamides / Q000494:pharmacology*
D003911:Dextrans; D005456:Fluorescent Dyes; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C015219:fluorescein isothiocyanate dextran; D013311:Streptozocin; D000068718:Rosuvastatin Calcium; D019821:Simvastatin; D003404:Creatinine; D016650:Fluorescein-5-isothiocyanate; D008798:Mevalonic Acid