title: Rosuvastatin ameliorates inflammation, renal fat accumulation, and kidney injury in transgenic spontaneously hypertensive rats expressing human C-reactive protein.
abstract: Recently, we derived "humanized" spontaneously hypertensive rats (SHR-CRP) in which transgenic expression of human CRP induces inflammation, oxidative stress, several features of metabolic syndrome and target organ injury. In addition, we found that rosuvastatin treatment of SHR-CRP transgenic rats can protect against pro-inflammatory effects of human CRP and also reduce cardiac inflammation and oxidative damage. In the current study, we tested the effects of rosuvastatin (5 mg/kg) on kidney injury in SHR-CRP males versus untreated SHR-CRP and SHR controls. All rats were fed a high sucrose diet. In SHR-CRP transgenic rats, treatment with rosuvastatin for 10 weeks, compared to untreated transgenic rats and SHR controls, was associated with significantly reduced systemic inflammation which was accompanied with activation of antioxidative enzymes in the kidney, lower renal fat accumulation, and with amelioration of histopathological changes in the kidney. These findings provide evidence that, in the presence of high CRP levels, rosuvastatin exhibits significant anti-inflammatory, anti-oxidative, and renoprotective effects.
authors.affiliation: Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. pravenec@biomed.cas.cz.
authors.forename: J
authors.initials: J
authors.lastname: Šilhavý
authors.forename: V
authors.initials: V
authors.lastname: Zídek
authors.forename: V
authors.initials: V
authors.lastname: Landa
authors.forename: M
authors.initials: M
authors.lastname: Šimáková
authors.forename: P
authors.initials: P
authors.lastname: Mlejnek
authors.forename: O
authors.initials: O
authors.lastname: Oliyarnyk
authors.forename: H
authors.initials: H
authors.lastname: Malínská
authors.forename: L
authors.initials: L
authors.lastname: Kazdová
authors.forename: M
authors.initials: M
authors.lastname: Mancini
authors.forename: M
authors.initials: M
authors.lastname: Pravenec
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000276:immunology; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D055647:Rats, Transgenic; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein