title: Renal protective effects of pitavastatin on spontaneously hypercholesterolaemic Imai Rats.
abstract: BACKGROUND
  Independent of their lipid-lowering effects, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have renal protective effects on various models of progressive renal diseases, therefore, additional therapeutic advantages have been considered. In the present study, using spontaneously hypercholesterolaemic Imai rats, we examined the protective effects of pitavastatin on renal injuries and the oxidative modification of the low-density lipoprotein (LDL) and high-density lipoprotein (HDL), since oxidized lipoproteins are speculated to be involved in the mechanism of this rat strain's renal injuries.
  
  
  METHODS
  Male Imai rats were treated with pitavastatin (n = 11) at a dose of 100 mg/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 4 weeks. At the end of the study, the effects of pitavastatin on the susceptibility of serum LDL and HDL to oxidation, and renal histology were examined.
  
  
  RESULTS
  Pitavastatin treatment did not affect hyperlipidaemia, but significantly reduced proteinuria and preserved creatinine clearance deterioration. At the end of the study, lag times for LDL and HDL oxidation were prolonged by the treatment of pitavastatin to 126 and 153%, respectively, compared with the controlled group. The glomerulosclerosis index (SI) for untreated controlled rats was significantly higher than that for the pitavastatin-treated group. An immunohistochemistry study showed significantly lower numbers of ED-1 positive macrophages in the glomeruli and interstitium in pitavastatin-treated rats compared with those controlled.
  
  
  CONCLUSIONS
  Pitavastatin treatment prevented renal injuries in Imai rats independent of lipid-lowering effects. Prevention of oxidative modification of LDL and HDL may play an important role on the beneficial effects of pitavastatin treatment.
authors.affiliation: Department of Nephrology, Qilu Hospital of Shandong University, Shandong Province, China.
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Liang
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Otani
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tone
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Fujii
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Mune
authors.forename: Susumu
authors.initials: S
authors.lastname: Yukawa
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001794:Blood Pressure; D001806:Blood Urea Nitrogen; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000473:pathology*; D006949:Hyperlipidemias / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008055:Lipids / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011804:Quinolines; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C108475:pitavastatin; D010100:Oxygen