Vol 12, Issue 3, 2019 Online - 2455-3891 Print - 0974-2441 POMEGRANATE ATTENUATES ACUTE GENTAMICIN-INDUCED NEPHROTOXICITY IN SPRAGUE-DAWLEY RATS: THE POTENTIAL ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS HAYDER M AL-KURAISHY * , ALI I AL-GAREEB, MARWA SALIH SADEK AL-NAIMI Department of Clinical Pharmacology, Medicine and Therapeutic, Medical Faculty, College of Medicine, Al-Mustansiriya University, P.O. Box 14132, Baghdad, Iraq. Email: hayderm36@yahoo.com Received: 19 November 2018, Revised and Accepted: 28 December 2018 ABSTRACT Objectives: Nephrotoxicity is a renal-specific situation in which the excretion of toxic metabolites is reduced due to toxic agents and drugs. Gentamicin is an antibiotic belongs to aminoglycoside group which may induce nephrotoxicity due to induction of oxidative stress. Pomegranate is a component of the traditional medicine called Punica granatum with significant nephron-protective effect. Therefore, the objective of the present study was to evaluate the nephronprotective effect of pomegranate in gentamicin-induced nephrotoxicity. Methods: A total of 30 male Sprague-Dawley rats were used which divided into Group 1 (n=10): Rats treated with distilled water 5 ml/kg plus normal saline 5 ml/kg for 12 days, Group 2 (n=10): Rats treated with distilled water 5 ml/kg plus gentamicin 100 mg/kg for 12 days, and Group 3 (n=10): Rats treated with pomegranate 100 mg/kg plus gentamicin 100 mg/kg for 12 days. Blood urea, serum creatinine, malondialdehyde (MDA), kidney injury molecule (KIM-1), and cystatin-C were measured in both control and experimental groups. Results: Rats treated with gentamicin showed nephrotoxicity as evident by significant elevation in serum creatinine, blood urea, serum creatinine, KIM-1, MDA, and cystatin-C sera levels. Pomegranate leads to significant reduction of blood urea and serum creatinine compared to gentamicin group, p<0.05. Pomegranate also reduced MDA, KIM-1, and cystatin-C sera levels significantly compared to gentamicin group, p<0.01. Conclusion: Pomegranate produced significant nephroprotective effect on gentamicin-induced nephrotoxicity through modulation of oxidative stress and inflammatory biomarkers. Keywords: Nephrotoxicity, Gentamicin, Pomegranate. INTRODUCTION Nephrotoxicity is a renal-specific circumstance due to toxic agents and drugs. About 20% of nephrotoxicity is induced and caused by drugs; this fraction is augmented in the old age due to ascend in the life span [1]. Gentamicin is an antibiotic of aminoglycoside group, used for the treatment of dissimilar bacterial infections. 90% of administrated gentamicin is excreted unchanged in the proximal renal tubule that leads to a necrosis at a higher dose [2]. An excess in the generation of reactive oxygen species (ROS) and free radicals is the main mechanism of gentamicin-induced nephrotoxicity. Absolutely, gentamicin induces the expression of transporter proteins at proximal renal tubules causing free radical generations [3]. As well, gentamicin-induced nephrotoxicity is a versatile incident which previously allied to the oxidative stress only. Chronic and high dose of gentamicin initiates in vitro and in vivo free radical productions and induction of oxidative stress. Gentamicin elicits mitochondrial superoxide anions that cause the generation of hydroxyl radicals [4]. Hence, antioxidant agents reveal a renoprotective effect in gentamicin- induced nephrotoxicity. Pomegranate peel contains 50% of bioactive constituents including flavonoids, phenolics, proanthocyanidin, and ellagitannins with different minerals. Pomegranate edible part contains 10% seeds and 40% arils, arils mainly enclose anthocyanins, while the seeds contain mainly anthocyanin and glucosides. The most important phytochemical in the pomegranate juice is an ellagitannin which also named punicalagin which inhibits peroxidation through scavenging of free radicals [5]. Pomegranate effect on free radicals is happened by different mechanism, it scavenges various types of free radicals such as ROS and reactive nitrogen species, and also, it inhibits ROS-generating enzymes including cyclooxygenase, lipoxygenase, and xanthine hydrogenase/ oxidase [6]. Therefore, the objective of the present study was to evaluate the nephroprotective effect of pomegranate on gentamicin-induced nephrotoxicity. METHODS A total number of 30 Sprague-Dawley male rats were used, rats age ranges from 3 to 4 months and their body weight ranges from 200 to 400 g. The animals were placed at appropriate temperature of 22–25°C with 12/12 hrs, light-dark cycle. They left 1 week for adaptation without any intervention with free access to normal chow pellets and water. Humane care for animals was according to the guide to the care and the use of laboratory animal. The rats were randomly divided into three groups, 10 rats in each group. Group 1 (n=10): Rats treated with distilled water (5 ml/kg, p.o) for 12 days, on day 6–12, they received an intraperitoneal (i.p.) injection of normal saline (5 ml/kg) daily. Group 2 (n=10): Rats treated with distilled water (5 ml/kg, p.o) for 12 days, and on day from 6 to 12, they received gentamicin 100 mg/kg, i.p. Group 3 (n=10): Rats treated with pomegranate (100 mg/kg, p.o) for 12 days, and on day 6–12, they received gentamicin 100 mg/kg, i.p at an interval of 1 h. On the 13 th day, rats were decapitated under light anesthesia, blood samples were obtained and serum was centrifugated at 3500 rpm/15 min. The method protocol was according to Singh et al. method [7]. © 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/ajpcr.2019.v12i3.30894 Research Article