ABSTRACT
This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning.
Subject(s)
Animals , Rats , Agmatine/pharmacology , Antioxidants/pharmacology , Chlorpromazine/toxicity , Oxidative Stress/drug effects , Prosencephalon/drug effects , Rats, WistarABSTRACT
Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a dose- and time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.
Subject(s)
Animals , Mice , Rats , Blood-Brain Barrier/metabolism , Brain Ischemia/metabolism , CA1 Region, Hippocampal/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Gerbillinae , Intracellular Signaling Peptides and Proteins/administration & dosage , Lipid Peroxidation , Malondialdehyde/metabolism , Neuroprotective Agents/administration & dosage , Oncogene Proteins/administration & dosage , Oxidative Stress , Prosencephalon/drug effects , Recombinant Fusion Proteins/administration & dosage , tat Gene Products, Human Immunodeficiency Virus/administration & dosageABSTRACT
The present experiments were done to determine the effectiveness of a non-specific nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on oxidative stress parameters induced by aluminium chloride (AlCl3) intrahippocampal injections in Wistar rats. Animals were sacrificed 3 h and 30 d after treatments, heads were immediately frozen in liquid nitrogen and forebrain cortices were removed. Crude mitochondrial fraction preparations of forebrain cortices were used for the biochemical analyses: nitrite levels, superoxide production, malondialdehyde concentrations, superoxide dismutase (SOD) activities and reduced glutathione contents. AlCl3 injection resulted in increased nitrite concentrations, superoxide anion production, malondialdehyde concentrations and reduced glutathione contents in the forebrain cortex, suggesting that AlCl3 exposure promoted oxidative stress in this brain structure. The biochemical changes observed in neuronal tissues showed that aluminium acted as a pro-oxidant. However, the non-specific nitric oxide synthase (NOS) inhibitor, L-NAME, exerted anti-oxidant actions in AlCl3-treated animals. These results revealed that NO-mediated neurotoxicity due to intrahippocampal AlCl3 injection spread temporally and spatially to the forebrain cortex, and suggested a potentially neuroprotective effect for L-NAME.
Subject(s)
Animals , Male , Rats , Aluminum Compounds/toxicity , Chlorides/toxicity , Glutathione/metabolism , Malondialdehyde , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitrites/chemistry , Prosencephalon/drug effects , Rats, Wistar , Superoxide Dismutase/metabolism , Superoxides/metabolismABSTRACT
It has been suggested that propofol has the protective effect on cerebral ischemia-reperfusion injury. The aim of this study is to evaluate the effect of propofol pretreatment on incomplete forebrain ischemia-reperfusion injury in rats. Thirty Sprague-Dawley rats were anesthetized with isoflurane in oxygen and randomly allocated into propofol group (n=13) and saline group (n=17). In propofol group, propofol was pretreated in a step-down scheme before inducing forebrain ischemia by occlusion of both common carotid arteries and arterial hypotension. After ischemia (20 min) and reperfusion (30 min), rats were decapitated. Brain was sliced to obtain coronal slices of 4-12 mm from frontal pole, which were reacted with 2% 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) for 10 min to differentiate the damaged tissues from normal tissues. Median (interquartile range) values of the average percent infarct area were 0.0 (8.6)% and 20.1 (41.2)% in propofol and saline groups, respectively. There was significant difference between the groups. In conclusion, propofol may have a protective effect on incomplete forebrain ischemia-reperfusion injury.