Effect of the HMG-CoA reductase inhibitor rosuvastatin on early chronic kidney injury in obese zucker rats fed with an atherogenic diet.
The obese Zucker rat (OZR) spontaneously develops hyperlipidemia, insulin resistance, and microalbuminuria. In this study, the initial metabolic, functional, and glomerular pathology in young OZR fed with an atherogenic diet resembles the characteristics of metabolic syndrome. Hyperlipidemia and other metabolic derangement cause early glomerular damage in OZR by 10 weeks of age, before overt diabetes is developed. Consequently, the effects of potential interventions should also be evaluated at the young age. In OZR fed with an atherogenic high-fat diet, low (5 mg/kg) and high (20 mg/kg) dosages of rosuvastatin started at 5 weeks and maintained for 10 weeks induced a significant improvement in metabolic abnormalities, blood pressure, and renal function, including microalbuminuria. The low dose of rosuvastatin significantly decreased mesangial expansion, and the high dose exerted a marked protective effect on the development of both glomerular hypertrophy and mesangial expansion. The statin also attenuated the inflammatory expression in the kidney cortex.
Reisin
Efrain
E
Section of Nephrology and Hypertension, Department of Internal Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA. ereisi@lsuhsc.edu
Ebenezer
Philip J
PJ
Liao
Jie
J
Lee
Benjamin S
BS
Larroque
Michelle
M
Hu
Xuejiao
X
Aguilar
Erwin A
EA
Morse
Stephen A
SA
Francis
Joseph
J
D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D017931:DNA Primers; D004041:Dietary Fats / Q000008:administration & dosage*; D005247:Feeding Behavior; D005455:Fluorescent Antibody Technique; D005464:Fluorobenzenes / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008055:Lipids / Q000097:blood / Q000145:classification; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
D017931:DNA Primers; D004041:Dietary Fats; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D008055:Lipids; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein