title: Why does atorvastatin inhibit renal crystal retention?
abstract: Recently, we reported that atorvastatin prevents renal tubular cell injury by oxalate and inhibits renal crystal retention. In this study, we investigated the mechanism by which atorvastatin inhibits renal crystal retention. Male Sprague-Dawley rats were separated into four experimental groups, and the ethylene glycol model of hyperoxaluria and the atorvastatin treatment model were analyzed. To clarify the mechanism by which atorvastatin inhibits renal crystal retention, the removed kidneys were used for the quantitative analysis of superoxide dismutase (SOD) and catalase. The subunits of the NADPH oxidase system were evaluated using real-time polymerase chain reaction analysis. Furthermore, the level of transforming growth factor-β (TGF-β) in kidney tissue was compared in each group. Atorvastatin treatment increased the SOD and catalase level compared with the stone-forming control group. Atorvastatin treatment decreased the expression of NOX-1 mRNA. Furthermore, the level of TGF-β was suppressed by atorvastatin treatment. We found that atorvastatin have inhibited calcium oxalate (CaOX) urolithiasis formation. We hypothesize that the mechanism of action of atorvastatin involves inhibiting TGF-β and NADPH oxidase, and increasing the SOD and catalase level. We believe that atorvastatin will be helpful in the treatment of CaOX urolithiasis.
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan. Tsujihata@uro.med.osaka-u.ac.jp
authors.forename: Masao
authors.initials: M
authors.lastname: Tsujihata
authors.forename: Iwao
authors.initials: I
authors.lastname: Yoshioka
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujimura
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okuyama
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002129:Calcium Oxalate / Q000737:chemistry; D002374:Catalase / Q000378:metabolism; D003460:Crystallization; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007669:Kidney Calculi / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics
chemical_list: D006538:Heptanoic Acids; D011758:Pyrroles; D016212:Transforming Growth Factor beta; D002129:Calcium Oxalate; D000069059:Atorvastatin; D002374:Catalase; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein