4.5 Article

Effect of the HMG-CoA Reductase Inhibitor Rosuvastatin on Early Chronic Kidney Injury in Obese Zucker Rats Fed With an Atherogenic Diet

Journal

AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Volume 338, Issue 4, Pages 301-309

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1097/MAJ.0b013e3181b27195

Keywords

Statin; Metabolic syndrome; Zucker rats; Renal function; Albuminuria; Glomerular injury

Funding

  1. AstraZeneca

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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 all 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 oil file development of both glomerular hypertrophy and mesangial expansion, The statin also attenuated the inflammatory expression in the kidney cortex.

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