Idacahyati et al. Int J App Pharm, Vol 13, Special Issue 3, 2021, 53-56 4 th International Seminar on Pharmaceutical Science and Technology 2020 | 53 NEPHROPROTECTIVE ACTIVITY OF ETHANOL EXTRACT OF KIRINYUH (CHROMOLAENA ODORATA L) IN GENTAMICIN INDUCED NEPHROTOXICITY IN WISTAR RATS Original Article KENI IDACAHYATI, LUSI NURDIANTI, SILVI SIPTANUL HUSNI, FIRMAN GUSTAMAN, WINDA TRISNA WULANDARI Departemen of Clinical Pharmacy and Pharmacology, Bakti Tunas Husada Institute of Health Science, Tasikmalaya, Indonesia Email: keniida@stikes-bth.ac.id Received: 25 Sep 2020, Revised and Accepted: 16 Oct 2020 ABSTRACT Objective: The global prevalence of Chronic Kidney Disease (CKD) was 9.1% (697.5 million cases). Chronic kidney disease can occur, one of which is caused by drug nephrotoxicity. Nephrotoxicity remains major problem for its effective long-term clinical use. Gentamicin is known to cause many morphologic, metabolic and functional alterations in the kidney and the specificity of gentamicin nephrotoxicity is related to its accumulation in the renal proximal convoluted tubules leading to tubular necrosis. Nephrotoxicity can be prevented by nephroprotective by giving antioxidants. Kirinyuh leaves (Chromolaena odorata L.) has potential as a nephroprotective because it contains chemical compounds that have antioxidant activity. Methods: Wistar rats as many as 25 animals were divided into five groups, namely the normal control negative control (gentamicin 60 mg/kg BW rat), and kirinyuh leaf extract at a dose of 225, 450 and 675 mg/kg BW treatment was carried out for 10 d. Serum creatinine and urea levels were evaluated along with histopathological investigation in various experimental groups of rats. Data analysis using the One Way Anova test and continued LSD test. Results: Serum creatinine was a significant difference between groups P = 0.000 (P<0.05). The results of LSD analysis on creatinine levels showed a significant difference between the normal group and the negative group (P = 0.00); negative group to dose group 1 (P = 0.020) (P<0.05); dose 2 (P = 0.005) (P<0.05); and dose 3 (P = 0.000) (P<0.05). Dose 3 had the lowest creatinine level compared to other dose groups. Conclusion: Serum creatinine level at dose 675 significantly changes compare by a negative group of other dose groups. Renal histopathology results showed that the group with a dose of 450 mg/BW of rats had the lowest necrosis rate compared to the negative control group and other dose groups. Keywords: Chronic kidney disease, Gentamycin, Nephroprotective, Kirinyuh © 2021 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2021.v13s3.11 Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Chronic kidney disease (CKD) is kidney damage and a decrease in Glomerular Filtration Rate (GFR) of less than 60 ml/min/1.73 m 2 for a minimum of 3 mo [1]. The prevalence of CKD globally is 13.4%, and 48% of people have decreased kidney function but do not need hemodialysis. Then as many as 96% of people experience kidney damage, but they are not aware of it [2]. In Indonesia, CKD increased prevalence in 2013, from 2% to 3.8% in 2018 [3]. Chronic kidney disease can be caused by drug nephrotoxicity. Gentamicin is an aminoglycoside antibiotic commonly used in clinical practice for the treatment of life-threatening Gram-negative bacterial infections can be restricted due to profound nephrotoxicity side effects [4]. Nephrotoxicity is a condition characterized by changes in cell morphofunctional such as impaired protein synthesis, increased lipid peroxidation process, decreased urine concentration capacity, tubular proteinuria, lowering of GFR and mitochondrial damage [5]. The mechanism of gentamicin causes nephrotoxicity by directly or indirectly activating the intrinsic apoptotic pathway by reducing the production of ATP and causing oxidative stress by increased free radical species such as superoxide anion (O2 - ), hydroxide anion (OH - ), and hydrogen peroxide (H2O2) in mitochondrial cells in the renal cortex. Mitochondrial DNA (mtDNA) is susceptible to oxidative damage by Reactive Oxygen Species (ROS), which continually increase within the mitochondrial matrix to cause cell death or necrosis. Gentamicin stimulates expression of inducible nitric oxide synthase (iNOS) and NO production in the isolated glomerulus, and mesangial cells contraction could be mediated by several mechanisms secretion of platelet-activating factor (PAF). The increase in available NO during the oxidative stress can react with superoxide anion, and peroxynitrite is created. The created peroxynitrite is further creating nitrosative stress and cytotoxicity [6]. Oxidative stress is a predisposing factor and direct cause of various disorders in both human and animals, including renal [7]. Nephrotoxicity can be prevented by the presence of nephroprotective adding natural antioxidants. Kirinyuh leaves have a high antioxidant activity that is with a concentration inhibitor value (IC50) of 9.5671 ppm and has an antioxidant capacity of 49.037% [8, 9]. The purpose of this study was to determine the antioxidant activity of kirinyuh leaves as a nephroprotective. MATERIALS AND METHODS Material Chemical materials Hydrochloric acid, 96% ethanol, gentamicin, formaldehyde, picric acid, glacial acetic acid, 10% NaOH, Mg, Mayer reagent, Wagner, Lieberman-Burchard, FeCl3, creatinine and urea reagent kit, CMC 1%, NaCl 0,9%, aqua dest. Formaldehyde 4%, xylol paraffin, Hematoxylin Eosin, NaOH, hydrochloric acid, sulfuric acid. Plant materials Kirinyuh Leaves were obtained from Cicarulang Village, Singaparna City, Tasikmalaya, West Java, Indonesia. They were determined by Herbarium Plant Taxonomy Laboratory of Biology Department, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Bandung. Extraction Kirinyuh leaves were collected and washed, cut, dried and powdered. He extracts were prepared by macerating a weighed amount 1000 g with 96% ethanol. The results of the extraction obtained as much as 3.5 L liquid extract then concentrated and received as much as 46 grams of extract. Rendement extract obtained was 4.6%. Phytochemical screening methode Detection of flavonoids Simplicia the powder was put into a test tube filled with water, then heated, then filtered, the filtrate obtained added to obtain International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 13, Special Issue 3, 2021