Simvastatin Improves Renal Function and Glomerulosclerosis in Ischemic-reperfusion Injury

Putu Nita Cahyawati, Desak Putu Oki Lestari, Ayu Savitri Siskayani, I Made Toya Ariawan

Abstract


BACKGROUND: Statin is an anti-cholesterol drug that is widely prescribed throughout the world. Statins are mainly used to treat and prevent cardiovascular disease. Several studies have found the pleiotropic effect of statin. However, related effect of statin in kidney failure is still unclear. Ischemic-reperfusion (I/R) injury is a major cause of acute kidney failure. This study aims to determine the effect of simvastatin on kidney function and glomerular conditions by periodic acid-schiff staining in I/R injury.

METHODS: Eighteen male Swiss mice were grouped into sham operation group (GSO), I/R injury group (GIRI), and simvastatin group (GSIM). The GSO group was performed by sham operation and pretreatment of 1% carboxymethylcellulose (CMC) for 3 days. The GIRI group was performed by I/R procedure and pretreatment of 1% CMC for 3 days and the GSIM group was performed by I/R procedure and pretreatment of 10 mg/kg BW simvastatin for 3 days. Blood urea nitrogen (BUN) and creatinine serum were assessed to determine kidney function. Histopathological analysis of glomerulosclerosis was assessed by the extent of glomerular damage (sclerosis), capillary loops, and synechia. The data were analyzed by one-way ANOVA followed by post hoc Tukey’s test (p<0.05).

RESULTS: The creatinine and BUN levels in the GIRI group were the highest (0.97±0.48) compared with the other groups. The glomerulosclerosis index in the GSO group was 0.75±0.56, the GIRI group was 3.55±0.61, and the GSIM group was 2.08±1.37. There was a significant difference in the glomerulosclerosis index between the GSO and GIRI groups, but there was no significant difference between the GIRI and GSIM groups. These differences include the formation of sclerosis in the glomerulus, capillary loop, and synechiae.

CONCLUSION: Simvastatin improves kidney function and glomerulosclerosis in I/R injury.

KEYWORDS: ischemic-reperfusion injury, simvastatin, glomerulosclerosis


Full Text:

PDF

References


Gazzerro P, Proto MC, Gangemi G, Malfitano AM, Ciaglia E, Pisanti S, et al. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacol Rev. 2012; 64: 102-46, CrossRef.

Tristano AG, Fuller K. Immunomodulatory effects of statins and autoimmune rheumatic diseases: novel intracellular mechanism involved. Int J Immunopharmaco. 2006; 6: 1833-46, CrossRef.

Pleşea CF, Tânţu M, Grigorescu A, Cîrlig V. Statins–between the cholesterol lowering and pleiotropic effect. Current Health Sciences Journal. 2013; 39: 210-3.

Yano M, Matsumura T, Senokuchi T, Ishii N, Murata Y, Taketa K. et al. Statins activate peroxisome proliferator-activated receptor through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase–dependent cyclooxygenase-2 expression in macrophages. Circ Res. 2007; 100: 1442-51, CrossRef.

Cahyawati PN, Ngatidjan, Sari DCR, Romi MM, Arfian N. Simvastatin attenuates renal failure in mice with a 5/6 subtotal nephrectomy. Int J Pharm Pharm Sci. 2017; 9: 12-7, CrossRef.

Santos FN, Watanabe M, Vasco CF, Fonseca CD, Vattimo MFF. Antioxidant protection of statins in acute kidney injury induced by sepsis. Rev Esc Enferm USP. 2014; 48: 820-6, CrossRef.

Brunelli SM, Waikar SS, Bateman BT, Chang TI, Lii J, Garg AX, et al. Preoperative statin use and postoperative acute kidney injury. Am J Med. 2012; 125: 1195-204, CrossRef.

Haynes R, Lewis D, Emberson J, Reith C, Agodoa L, Cass A, et al. Effects of lowering LDL cholesterol on progression of kidney disease. J Am Soc Nephrol 25. 2014; 25: 1825-33, CrossRef.

Dormuth CR, Hemmelgarn BR, Paterson JM, James MT, Teare GF, Raymond CB, Lafrance JP, et al. Use of high potency statins and rates of admission for cute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ. 2013; 346: f880, CrossRef.

Layton JB, Brookhart A, Funk MJ, Simpson RJ, Pate V, Stürmer T, et al. Acute kidney injury in statin initiators. Pharmacoepidemiol Drug Saf. 2013; 22: 1-21, CrossRef.

Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. J Renal Inj Prev. 2015; 4: 20-7, CrossRef.

Gueler F, Park JK, Rong S, Kirsch T, Lindschau C, Zheng W, et al. Statins attenuate ischemia-reperfusion injury by inducing heme oxygenase-1 in infiltrating macrophages. Am J Pathol. 2007; 170: 1192-9, CrossRef.

Rahman M, Shad F, Smith MC. Acute kidney injury: a guide to diagnosis and management. Am Fam Physician. 2012; 86: 631-9, PMID.

Ostermann M, Cerdá J. The burden of acute kidney injury and related financial issues. Contrib Nephrol. 2018; 193: 100-12, CrossRef.

Cahyawati PN. Effect of simvastatin on histopathology of the heart after 5/6 subtotal nephrectomy. Int J App Pharm. 2019; 1: 131-3, CrossRef.

Williams P, Lopez H, Britt D, Chan C, Ezrin A, Hottendorf R. Characterization of renal ischemia-reperfusion injury in rats. J Pharmacol Toxicol Methods. 1997; 37: 1-7, CrossRef.

Fogo AB. Progression and potential regression of glomerulosclerosis. Kidney Int. 2001; 59: 804-19, CrossRef.

Nogueira A, Pires MJ, Oliveira PA. Pathophysiological mechanisms of renal fibrosis: a review of animal models and therapeutic strategies. In Vivo. 2017; 31: 1-22, CrossRef.

Teshima CAS, Watanabe M, Fonseca CD, Vattimo MFF. Simvastatin and acute ischemic renal injury in rats. Acta Paulista de Enfermagem. 2012; 25: 86-9, CrossRef.

Sharyo S, Yokota-Ikeda N, Mori M, Kumagai K, Uchida K, Ito K, et al. Pravastatin improves renal ischemia–reperfusion injury by inhibiting the mevalonate pathway. Kidney International. 2008; 7: 577-84, CrossRef.

Christensen M, Su AW, Snyder RW, Greco A, Lipschutz JH, Madaio MP. Simvastatin protection against acute immunemediated glomerulonephritis in mice. Kidney International. 2006; 69: 457-63, CrossRef.

Vogt L, Bangalore S, Fayyad R, Melamed S, Hovingh GK, DeMicco DA, et al. Atorvastatin has a dose‐dependent beneficial effect on kidney function and associated cardiovascular outcomes: post hoc analysis of 6 double‐blind randomized controlled trials. J Am Heart Assoc. 2019; 8: e010827, CrossRef.




DOI: https://doi.org/10.18585/inabj.v12i2.1082

Indexed by:

                 

                  

               

     

 

The Prodia Education and Research Institute