International Journal of Applied Pharmaceutics ISSN - 0975 - 7058 Vol 11, Special Issue 5, 2019 EFFECT OF SIMVASTATIN ON HISTOPATHOLOGY OF THE HEART AFTER 5/6 SUBTOTAL NEPHRECTOMY PUTU NITA CAHYAWATI* Department of Pharmacology and Pharmacy, Faculty of Medicine and Health Sciences, Warmadewa University, Bali, Indonesia. Email: putunitacahyawati@gmail.com Received: May 6, 2019, Revised and Accepted: July 20, 2019 ABSTRACT Objective: This study aims to assess the condition of cardiac histopathology through hematoxylin-eosin staining in 5/6 subtotal nephrectomy conditions. Methods: Fifteen male Swiss mice aged 3–5 months will be grouped into 3 treatment groups, namely the nephrectomy group (JSN, n=5), sham operation (JSO, n=5), and simvastatin 20 mg/kg body weight (JSIM, n=5). The histopathology of the heart will be assessed blindly. Severity is assessed based on scoring using a scale (−) no damage, (+) mild, (++) medium, and (+++) heavy. Assessment of severity refers to the irregularity of the heart muscle, increased amount of connective tissue, myofibril hypertrophy, myofibril swelling, sarcoplasmic fragmentation, sarcoplasmic vacuolization, bleeding in a myofibril, myofibril degeneration, cardiomyocyte damage, and the presence of acidophilic cytoplasm. Results: The results showed no morphological changes in heart muscle tissue in the JSO group except for fragmentation and vacuolization in minimal amounts of sarcoplasm (+), whereas in the JSN and JSIM groups, there was moderate damage to sarcoplasm (++) and minimal changes in myofibrils (hypertrophy and bleeding) (+). The JSN group also found severe damage (+++) to the irregularity of the heart muscle, whereas in JSIM, only moderate damage was found (++) to the irregularity of the heart muscle. Conclusion: Simvastatin seems to be able to correct the irregularity of the heart muscle in the condition of 5/6 subtotal nephrectomy. Keywords: Cardiac histopathology, Subtotal 5/6 nephrectomy, Simvastatin, Myofibrils. INTRODUCTION Cardiovascular disease is a condition that often occurs in patients with chronic renal failure (CRF). This condition increases the risk of death in patients. The prevalence of this disease also increases with increasing severity of kidney function [1-3]. The cardiovascular events that often occur are heart failure. This disease is estimated to have affected 23 million world populations, where the prevalence was higher in CRF patients than without CRF (63% vs. 5.8%) [3-5]. In the United States, this disease is the main cause of hospitalization [6]. Statins are very potent 3-hydroxy-3-methyl-3-methylglutaryl- coenzyme A reductase inhibitors. Besides its ability to inhibit cholesterol biosynthesis and reduce serum levels of low-density lipoprotein (LDL) cholesterol, statins have also been reported to have pleiotropic effects such as anti-inflammatory, antioxidants and improve endothelial function and angiogenesis. Statins are widely used in chronic ischemic heart disease and show improvement in endothelial function through increased production of endogenous nitric oxide, C-reactive protein, oxidized LDL, and cytokines such as tumor necrosis factor α and interleukin-6 [7]. Heart failure is characterized by systemic and vascular inflammation characterized by an increase in inflammatory biomarker and adhesion molecules [6]. The previous study shows that simvastatin therapy for 14 days was able to improve the fibrosis condition. However, the exact mechanism is not yet known [8]. For this reason, further research is needed to assess the condition of heart histopathology in more detail. This study aims to determine the histopathology of the heart in the CRF condition using animal models. METHODS Drug Simvastatin (Sigma-Aldrich, Singapore) was dissolved in a 1% solution of carboxymethyl cellulose (CMC) (Sigma-Aldrich, St Louis, USA). Simvastatin is given orally once a day for 14 days. Animals In this study, eighteen male Swiss mice with weighing 30–40 g were purchased from the experimental animal research center, Universitas Udayana, Denpasar. All mice were housed according to the treatment group at room temperature about 22±2°C and humidity about 50±5% with a 12–12 h light-dark cycle. They had free access to tap water and about 3–5 g standard food per day. This study was approved by Komite Etik Penelitian Fakultas Kedokteran Universitas Udayana/Rumah Sakit Umum Pusat Sanglah Denpasar No: 2125/UN14.2.2.VII.14/LP/2018. Experimental protocol All mice were randomized and acclimatized for 7 days. The mice were grounded according to the treatment group. Mice were divided in three groups (n=6) including sham group (JSO, group with only incision on the both sides of the flank region but there is no intervention on the kidney and 1% CMC solution), 5/6 subtotal nephrectomy group (JSN, group with nephrectomy on right kidney and ablation on superior and inferior part of the left kidney and simvastatin 20 mg/kg body weight [BW]), and simvastatin group (JSIM, group with 5/6 subtotal nephrectomy group and simvastatin 20 mg/kg BW) [9,10]. Animals were anesthetized using a combination of ketamine (90 mg/kg BW) and xylazine (10 mg/kb BW) through intraperitoneal injection. At the end of the study, the hearts were obtained from all the animals. © 2019 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ijap.2019.v11s5.T0105 4 th International Conference on Pharmacy and Pharmaceutical Science (ICPPS) 2019 Research Article