SIMVASTATIN ATTENUATES RENAL FAILURE IN MICE WITH A 5/6 SUBTOTAL NEPHRECTOMY

  • 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

Abstract

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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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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