We have studied the effect of resveratrol on lipoperoxidation and antioxidant enzyme activity level in the brain of healthy rats. When intraperitoneally administered, resveratrol significantly and dose dependently decreased brain malondialdehyde level. Resveratrol also increased in a dose-dependent way brain superoxide dismutase, catalase and peroxidase activities. Optimal effect on antioxidant enzyme and lipoperoxidation products were obtained with resveratrol concentration of 12.5 mg/kg body wt. Native polyacrylamide gel electrophoresis analysis of antioxidant isoenzymes revealed that resveratrol up regulated at least two acidic superoxide dismutase isoforms called A(1) and A(2), two basic isoforms called B(1) and B(2). Resveratrol also up regulated two catalase isoforms and a broad peroxidase band corresponding to several isoforms. All these findings suggest that resveratrol is able to cross the blood brain barrier and exerts potent antioxidant features. Resveratrol also exerts neuroprotective properties by up regulating several detoxifying enzymes, most of which are iron proteins.
J. Neurochem. (2011) 118, 416–428.
Abstract
Oxidative stress, resulting from accumulation of reactive oxygen species (ROS), plays a critical role on astrocyte death associated with neurodegenerative diseases. Astroglial cells produce endozepines, a family of biologically active peptides that have been implicated in cell protection. Thus, the purpose of the present study was to investigate the potential protective effect of one of the endozepines, the octadecaneuropeptide ODN, on hydrogen peroxide (H2O2)‐induced oxidative stress and cell death in rat astrocytes. Incubation of cultured astrocytes with graded concentrations of H2O2 for 1 h provoked a dose‐dependent reduction of the number of living cells as evaluated by lactate dehydrogenase assay. The cytotoxic effect of H2O2 was associated with morphological modifications that were characteristic of apoptotic cell death. H2O2‐treated cells exhibited high level of ROS associated with a reduction of both superoxide dismutases (SOD) and catalase activities. Pre‐treatment of astrocytes with low concentrations of ODN dose‐dependently prevented cell death induced by H2O2. This effect was accompanied by a marked attenuation of ROS accumulation, reduction of mitochondrial membrane potential and activation of caspase 3 activity. ODN stimulated SOD and catalase activities in a concentration‐dependent manner, and blocked H2O2‐evoked inhibition of SOD and catalase activities. Blockers of SOD and catalase suppressed the effect of ODN on cell survival. Taken together, these data demonstrate for the first time that ODN is a potent protective agent that prevents oxidative stress‐induced apoptotic cell death.
Ischemic stroke is a leading cause of long lasting disability in humans and oxidative stress an important underlying cause. The present study aims to determine the effect of short term (seven-days) administration of high dosage grape seed and skin extract (GSSE 2.5 g/kg) on ischemia/reperfusion (I/R) injury in a rat model of global ischemia. Ischemia was induced by occlusion of the common carotid arteries for 30 min followed by one-hour reperfusion on control or GSSE treated animals. I/R induced a drastic oxidative stress characterized by high lipid and protein oxidation, a drop in antioxidant enzyme defenses, disturbed transition metals as free iron overload and depletion of copper, zinc and manganese as well as of associated brain enzyme activities as glutamine synthetase and lactate dehydrogenase. I/R also induced NO and calcium disruption and an increase in calpain activity, a calcium-sensitive cysteine protease. Interestingly, almost all I/R-induced disturbances were prevented by GSSE pretreatment as oxidative stress, transition metals associated enzyme activities, brain damage size and histology. Owing to its antioxidant potential, high dosage GSSE protected efficiently the brain against ischemic stroke and should be translated to humans.
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