The Modulatory Effect of Metformin on Ethanol-Induced Anxiety, Redox Imbalance, and Extracellular Matrix Levels in the Brains of Wistar Rats

J Mol Neurosci. 2020 Dec;70(12):1943-1961. doi: 10.1007/s12031-020-01593-w. Epub 2020 Jul 3.

Abstract

The study investigated the potential neuroprotective effects of metformin (MET) on alcohol-induced neurotoxicity in adult Wistar rats. The animals were randomized in four groups (n = 10): control, alcohol (ALC), ALC + MET, and MET. ALC (2 g/kg b.w.) and MET (200 mg/kg b.w.) were orally administered for 21 days, once daily. For the ALC + MET group, MET was administered 2 h after ALC treatment. On day 22, the open field test (OFT) and elevated plus maze (EPM) were performed. MET improved global activity and increased the time spent in unprotected open arms, decreased oxidative stress, both in the frontal lobe and in the hippocampus, and increased neuroglobin expression in the frontal cortex. Histopathologically, an increased neurosecretory activity in the frontal cortex in the ALC + MET group was noticed. Thus, our findings suggest that metformin has antioxidant and anxiolytic effects and may partially reverse the neurotoxic effects induced by ethanol.

Keywords: Alcohol; Anxiety; Metformin; Neuroglobin; Oxidative stress; Rats.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Anxiety / drug therapy*
  • Anxiety / etiology
  • Brain / drug effects*
  • Brain / metabolism
  • Ethanol / toxicity
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Male
  • Maze Learning
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Neuroglobin / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress
  • Rats
  • Rats, Wistar

Substances

  • Antioxidants
  • Neuroglobin
  • Neuroprotective Agents
  • Ethanol
  • Metformin