Neuroprotective effects of gallic acid against hypoxia/reoxygenation-induced mitochondrial dysfunctions in vitro and cerebral ischemia/reperfusion injury in vivo

Brain Res. 2014 Nov 17;1589:126-39. doi: 10.1016/j.brainres.2014.09.039. Epub 2014 Sep 22.

Abstract

Oxidative stress and mitochondrial dysfunction are frequently implicated in the pathology of secondary neuronal damage following cerebral ischemia/reperfusion. Recent evidence suggests that gallic acid (GA) reverses oxidative stress in rat model of streptozotocin-induced dementia, but the roles and mechanisms of GA on cerebral ischemia/reperfusion injury remain unknown. Here we investigated the potential roles and mechanisms of GA in hypoxia/reoxygenation induced by sodium hydrosulfite (Na2S2O4) in vitro and cerebral ischemia/reperfusion induced by middle cerebral artery occlusion (MCAO) in vivo. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazol carbocyanine iodide (JC-1), Dichlorofluorescin diacetate (DCF-DA) and MitoSOX fluorescent assay, Clark-type oxygen electrode, firefly luciferase assay, and calcium-induced mitochondrial swelling were conducted to detect cell death, mitochondrial membrane potential (MMP), intracellular and mitochondrial reactive oxygen species (ROS), oxygen consumption, ATP level, and mitochondrial permeability transition pore (MPTP) viability. We firstly find that modulation of the mitochondrial dysfunction is an important mechanism by GA attenuating hypoxia/reoxygenation insult. To further assess the effects of GA on cerebral ischemia/reperfusion injury, 2, 3, 5-triphenyl-tetrazolium chloride (TTC) staining, dUTP nick-end labeling (TUNEL) assay, and Cytochrome C (Cyt C) release were performed in MCAO rats. The results support that GA is useful against cerebral ischemia/reperfusion injury as a potential protective agent.

Keywords: Cerebral ischemia/reperfusion injury; Gallic acid; Hypoxia/reoxygenation injury; Mitochondrial dysfunction; Mitochondrial permeability transition pore.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Gallic Acid / pharmacology*
  • Gallic Acid / therapeutic use
  • Hypoxia / metabolism*
  • Infarction, Middle Cerebral Artery / metabolism*
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / prevention & control
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondrial Membrane Transport Proteins / drug effects
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Oxygen
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control

Substances

  • Mitochondrial Membrane Transport Proteins
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • mitochondrial permeability transition pore
  • Gallic Acid
  • Oxygen