Effect of pravastatin on cisplatin-induced nephrotoxicity in rats

被引：9

作者：

Fujieda, Mikiya ^{[1
]}

Morita, Taku ^{[1
]}

Naruse, Keishi ^{[2
]}

Hayashi, Yoshihiro ^{[3
]}

Ishihara, Masayuki ^{[1
]}

Yokoyama, Tadafumi ^{[4
]}

Toma, Tomoko ^{[4
]}

Ohta, Kazuhize ^{[4
,5
]}

Wakiguchi, Hiroshi ^{[1
]}

机构：

[1] Kochi Univ, Kochi Med Sch, Dept Pediat, Nanko Ku, Kochi 7838505, Japan

[2] Natl Kochi Hosp, Dept Clin Lab, Kochi, Japan

[3] Kochi Univ, Kochi Med Sch, Dept Pathol 1, Nanko Ku, Kochi 7838505, Japan

[4] Kanazawa Univ, Grad Sch Med, Dept Pediat, Kanazawa, Ishikawa, Japan

[5] Natl Kanazawa Med Ctr, Dept Pediat, Kanazawa, Ishikawa, Japan

来源：

HUMAN & EXPERIMENTAL TOXICOLOGY | 2011年 / 30卷 / 07期

关键词：

pravastatin; cisplatin; oxidative stress; triglyceride; p53; ISCHEMIA-REPERFUSION INJURY; ACUTE-RENAL-FAILURE; GLUTATHIONE-PEROXIDASE; SUPEROXIDE ANION; HEME OXYGENASE-1; TUBULAR CELLS; SIMVASTATIN; INHIBITION; DAMAGE; ATORVASTATIN;

D O I：

10.1177/0960327110376551

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

We investigated whether pravastatin ameliorates renal damage induced by cisplatin (CP). Forty-three male Wistar rats were divided into four groups: rats treated with a control diet for 19 days and saline injection on day 14 (group 1), group 1 with pravastatin treatment with 19 days (group 2), group 1 with CP injection on day 14 (group 3), and group 2 with CP injection (group 4). Renal function and serum lipids, renal malondialdehyde (MDA) and glutathione (GSH) levels, glutathione peroxidase (GPx) mRNA expression and activity, and kidney triglyceride (TG) concentrations were measured. Histology was evaluated by light microscopy with immunohistochemistry for p53, p53-upregulated modulation of apoptosis (PUMA), and terminal deoxynucleotide transferase dUTP nick end-labeling (TUNEL) staining. CP induced renal tubular damage with a higher MDA level, increased PUMA expression, p53- and TUNEL-positive cells counts, elevation of serum lipids, and decreased GSH level, GPx mRNA expression, and activity. Pravastatin partially ameliorated CP-induced renal injury, based on suppression of the renal MDA and TG levels, decreased p53 expression, and apoptosis in CP-treated rats. These findings suggest that pravastatin has a partial protective effect against CP nephrotoxicity via antioxidant activity as well as attenuation of the p53 response, and lipid-lowering effects.

引用

页码：603 / 615

页数：13

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