The possible neuroprotective effect of ellagic acid on sodium arsenate-induced neurotoxicity in rats

Life Sci. 2018 Apr 1:198:38-45. doi: 10.1016/j.lfs.2018.02.022. Epub 2018 Feb 15.

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 neurotoxicity 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.

Keywords: Ellagic acid; Neuroprotection; Oxidative stress; Rat; Sodium arsenite.

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / metabolism
  • Arsenates / toxicity*
  • Behavior, Animal
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Injuries / prevention & control
  • Ellagic Acid / pharmacology*
  • Glutathione Peroxidase / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • Maze Learning
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Arsenates
  • IL1B protein, rat
  • Interleukin-1beta
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Ellagic Acid
  • Nitric Oxide
  • sodium arsenate
  • Glutathione Peroxidase