• Putu Nita Cahyawati 1Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Ngatidjan . Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Dwi Cahyani Ratna Sari Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Muhammad Mansyur Romi Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Nur Arfian Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Muhammad Mansyur Romi Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Muhammad Mansyur Romi Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Nur Arfian Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Nur Arfian Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia


Objective: The objective of this study to investigate the effect of simvastatin on kidney fibrosis in mice with a 5/6 subtotal nephrectomy.

Methods: Thirty adults (3 mo old) male Swiss mice were submitted to a 5/6 subtotal nephrectomy and studied after 14 d. Animals were divided into five groups: 5/6 subtotal nephrectomy (SN, n=6), sham operation (SH, n=6), simvastatin 5.2 mg/kg body weight (SIM-1, n=6), simvastatin 10.4 mg/kg body weight (SIM-2, n=6), and simvastatin 20.8 mg/kg body weight (SIM-3, n=6) groups. At sacrifice, kidneys were harvested for morphology (glomerulosclerosis (GS), tubular injury and interstitial fibrosis), immunostaining (α-smooth muscle actin (α-SMA)) and platelet-derived growth factor receptor beta (PDGF-Rβ) and reverse transcriptase-polymerase chain reaction (RT-PCR) (MCP-1, ICAM-1, nephrin, and podocin) analysis.

Results: Glomerulosclerosis, tubular injury and interstitial fibrosis in the simvastatin group was significantly lower than SN group (p<0.05). Simvastatin significantly reduced α-SMA expression (3.61±1.06 vs 7.91±1.26, p<0.05, SIM-1 vs SN; 2.86±0.61 vs 7.91±1.26, p<0.05, SIM-2 vs SN; 1.71±0.50 vs 7.91±1.26, p<0.05, SIM-3 vs SN), MCP-1 was markedly expressed in the 5/6 subtotal nephrectomy kidneys and was reduced with simvastatin (1.4±0.64 vs 0.57±0.23, p<0.05, SN vs SIM-1; 1.4±0.64 vs 0.6±0.26, p<0.05, SN vs SIM-2; 1.4±0.64 vs 0.52±0.21, SN vs SIM-3, p<0.05). Simvastatin did not increase nephrin expression, but it increased podocin expression significantly in the SIM-3 group.

Conclusion: Simvastatin significantly attenuated GS, tubular injury and interstitial fibrosis through the downregulation of myofibroblast expansion and inflammatory mediators in mice with a 5/6 subtotal nephrectomy.

Keywords: Simvastatin, Kidney fibrosis, Inflammatory mediator, Myofibroblast, Subtotal nephrectomy


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How to Cite
Cahyawati, P. N., N. ., D. C. R. Sari, M. M. Romi, N. Arfian, M. M. Romi, M. M. Romi, N. Arfian, and N. Arfian. “SIMVASTATIN ATTENUATES RENAL FAILURE IN MICE WITH A 5/6 SUBTOTAL NEPHRECTOMY”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 9, no. 5, May 2017, pp. 12-17, doi:10.22159/ijpps.2017v9i5.12261.
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