Abnormalities in the lipid metabolism are suggested to take place in the progression of the renal injury. It has been reported that 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors show renal protective effects on various models of progressive renal injury even independent of lipid-lowering effect. We conducted an examination on spontaneously hypercholesterolemic (SHC) rats, trying to find out whether pitavastatin, a new HMG-CoA reductase inhibitor, could prevent the progression of renal injury. Oxidative susceptibilities of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were also analyzed, since oxidatively modified lipoproteins were expected to be available in the mechanism of the renal injury progression in SHC rat. Male SHC rats were treated with pitavastatin (n=11) at a dose of 100mg/kg-diet or received no specific therapy as controls (n=11) from 10 to 22 weeks of age. Body weight, urinary protein excretion, and serum constituents were evaluated every four weeks. At the end of the study, the effects of pitavastatin on the susceptibility of serum LDL and HDL to oxidation, renal histology and immunohistochemistry were examined. Pitavastatin treatment significantly reduced proteinuria (251±40 vs. 320±85 mg/24h, p<0.05, at 22 weeks) and preserved creatinine clearance deterioration (0.28±0.018 vs. 0.20±0.024 ml/min/100gBW, p<0.05, at 22 weeks) as compared with control. The levels of total cholesterol and triglycerides of both groups were the same. However, lag times of LDL and HDL oxidation were prolonged by the treatment of pitavastatin to 126% and 153% respectively as compared with the controls. Histological examination indicated that glomerulosclerosis index (SI) was much lower in the pitavastatintreated group than the controlled group (96 ± 22 vs. 138 ± 27, p<0.01). Macrophage infiltrations into glomeruli and interstitium were also suppressed in the pitavastatin-treated group. In conclusion, pitavastatin treatment prevented renal injury in SHC rats independent of the lipidlowering effect. Improvement of oxidative susceptibilities of LDL and HDL may play an important role in the beneficial effects of pitavastatin treatment.
|Number of pages||6|
|Journal||Journal of the Wakayama Medical Society|
|Publication status||Published - 2004 Dec 1|
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