Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie The possible neuroprotective effect of ellagic acid on sodium arsenate- induced neurotoxicity in rats Mehdi Goudarzi a,b , Shivasadat Amiri c , Ali Nesari d , Azam Hosseinzadeh e , Esrafil Mansouri f , Saeed Mehrzadi g, ⁎ a Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran b Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran c Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran d Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran e Air Pollution Research Center, Iran University of Medical Sciences, Tehran, Iran f Cellular and Molecular Research Center, Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran g Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran ARTICLE INFO Keywords: Sodium arsenite Ellagic acid Oxidative stress Neuroprotection Rat ABSTRACT Objective: Arsenic is a well-known environmental contaminant, causing toxicity in different organs. The aim of this study was to investigate the possible neuroprotective effect of ellagic acid (EA) on arsenic-induced neuro- toxicity in rats. Design: Animals were divided into five groups. The first group received normal saline (2 mL/kg) for 21 days as control group. Group 2 was orally treated with sodium arsenite (SA, 10 mg/kg) for 21 days. Groups 3 and 4 were orally treated with SA (10 mg/kg) for 7 days prior to EA (10 and 30 mg/kg respectively) treatment and continued up to 21 days simultaneously with SA administration. Group 5 was orally treated with EA (30 mg/kg) for 14 days. Passive avoidance test and rotarod test were done to evaluate the behavioral changes following SA and/ or EA treatment. Different biochemical, histological and molecular biomarkers were assessed in the brain tissue. Results: Our data showed that SA significantly elevated brain tissue arsenic levels and malondialdehyde, nitric oxide, protein carbonylation, tumor necrosis factor-alpha, and interlukein-1β production. A decrease in the total antioxidant capacity, reduced glutathione content and glutathione peroxidase activity occurred in the brain of rats exposed to SA. SA-treated rats showed a significant impairment in long-term-memory, motor coordination and equilibrium. These results were supported by histopathological observations of the brain. Results revealed that administration of EA (30 mg/kg) reversed all neural markers alternation and ameliorated behavioral and histopathological changes induced by SA. Conclusion: EA can effectively protect brain tissue against SA-induced neurotoxicity via its antioxidant and anti- inflammatory effects. 1. Introduction Nowadays, industrialization of societies and expansion of factories has dramatically increased the amount of contaminants and environ- mental pollutions. Arsenic is one of the most important worldwide environmental toxicants, which is found in air, water and soil. Arsenic is mainly distributed in the environment through using pesticides and herbicide, burning coal and treated wood, mining wastes, smelting metal and glass [27,44]. The main exposure to arsenic is occupational and the most frequent reason of poisoning is the use of contaminated water. Long term exposure to arsenic and its metabolites can cause skin and lung cancer, neurological effects, hypertension and cardiovascular diseases [9,42,51]. Since arsenic can cross the blood brain barrier (BBB), it accumulates in the brain and causes neurobehavioral ab- normalities. The neurotoxicity of arsenic includes symmetrical periph- eral neuropathy, decreased muscle strength, paralysis, sleep dis- turbances, delirium, confusion, disorientation, severe agitation, paranoid ideation, emotional liability, blurred vision, loss of hearing and taste as well as impairment of superior neurological functions such as learning, recent memory and concentration [21,27]. Although the exact mechanism of arsenic neurotoxicity is not clear, the evidence suggests that arsenic induces ROS-mediated oxidative https://doi.org/10.1016/j.lfs.2018.02.022 Received 2 January 2018; Received in revised form 5 February 2018; Accepted 14 February 2018 ⁎ Corresponding author at: Razi Drug Research Center, Iran University of Medical Sciences, P.O. Box: 1449614535, Tehran, Iran. E-mail address: mehrzadi.s@iums.ac.ir (S. Mehrzadi). Life Sciences 198 (2018) 38–45 Available online 15 February 2018 0024-3205/ © 2018 Elsevier Inc. All rights reserved. T