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.