Amelioration of cisplatin-induced nephrotoxicity by statins

Abstract

Objectives: This study aimed to investigate the protective effect of simvastatin (SIM) and rosuvastatin (RST) on cisplatin (CIS)-induced nephrotoxicity.

Materials and methods: Adult female Wistar rats were divided into six groups: control group (Group 1) received 0.5% sodium carboxy methyl cellulose, group 2 and group 3 received SIM and RST for 10 days, respectively, and group 4 was injected single dose of CIS (7 mg/kg, i.p.). Group 5 and 6 were treated with SIM (10 mg/kg, p.o.) and RST (10 mg/kg, p.o.) for 10 days, respectively. All groups received cisplatin on the 5(th) day of treatment. Renal function tests like serum creatinine, urea, BUN, albumin, calcium, uric acid and magnesium, serum lipids, and markers of oxidative stress such as renal malondialdehyde (MDA) level and superoxide dismutase (SOD) and catalase (CAT) activities were measured. All tissues were investigated for histopathological changes.

Result: CIS reduced the renal function, which was reflected with significant increase in serum urea, BUN, serum creatinine, uric acid and also significant decrease serum calcium, magnesium, albumin levels. In addition, cisplatin caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity, and elevation of serum lipids. SIM or RST ameliorate CIS induced renal damage due to improvement in renal function, oxidative stress, suppression of serum lipids, and histological alteration.

Conclusions: This finding suggests that simvastatin and rosuvastatin may have a protective effect against cisplatin-induced kidney damage via amelioration of lipid peroxidation as well as due to improvement of renal function, and lipid-lowering effects.

Keywords: Cisplatin; nephrotoxicity; rosuvastatin; simvastatin.

Figure 1

Effect of simvastatin and rosuvastatin on biomarkers of oxidative stress: (a) MDA, (b) SOD, and (c) CAT activity, #P< 0.05, ##P< 0.01, ###P< 0.001 vs. control; *P< 0.05, **P< 0.01, ***P< 0.001 vs. cisplatin

Figure 2

Light microscopy of kidney tissues from rats (HE stained kidney sections). (A) Control group, (B) Simvastatin group, (C) Rosuvastatin, (D) Cisplatin. Shows severe glomerular degeneration (arrow) and degeneration in tubular cells (asterisks), (E) Cisplatin + Simvastatin, (F) Cisplatin + Rosuvastatin