cytochrome-c-t and astaxanthine

Oxidative stress has been implicated in the pathogenesis of neurodegenerative disorders, such as vascular cognitive impairment (VCI). The present study was performed to investigate the potential neuroprotective effect of the antioxidant astaxanthin (ATX) in a mouse model of VCI. VCI was induced in male ICR mice by repeated occlusion of the bilateral common carotid artery, leading to repeated cerebral ischemia/reperfusion (IR) injury. After surgery, the mice received ATX or an equal volume of vehicle by daily intragastric administration for 28days. The results showed that ATX treatment ameliorated learning and memory deficits after repeated cerebral IR. ATX administration rescued the number of surviving pyramidal neurons in the CA1 and CA3 regions. The concentration of malondialdehyde was decreased, and the levels of reduced glutathione and superoxide dismutase in the hippocampus were increased. Electron microphotography revealed that damage to the ultrastructure of neurons was also reduced by ATX administration. In addition, the expression levels of Cytochrome C (Cyt C), cleaved Caspase-3 and Bax were lower and the expression of Bcl-2 was higher compared to control IR mice. Our findings demonstrate that ATX is able to suppresse learning and memory impairment caused by repeated cerebral IR and that this effect is associated with attenuation of oxidative stress.

Topics: Animals; Antioxidants; Apoptosis; Brain Ischemia; Cytochromes c; Dementia, Vascular; Disease Models, Animal; Glutathione; Hippocampus; Learning; Male; Malondialdehyde; Maze Learning; Memory Disorders; Mice; Mice, Inbred ICR; Neurons; Neuroprotective Agents; Oxidative Stress; Reperfusion; Reperfusion Injury; Superoxide Dismutase; Xanthophylls

Oxidative stress plays an important role in the neuronal damage induced by epilepsy. The present study assessed the possible neuroprotective effects of astaxanthin (ATX) on neuronal damage, in hippocampal CA3 neurons following amygdala kindling. Male Sprague-Dawley rats were chronically kindled in the amygdala and ATX or equal volume of vehicle was given by intraperitoneally. Twenty-four hours after the last stimulation, the rats were sacrificed by decapitation. Histopathological changes and the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and reduced glutathione (GSH) were measured, cytosolic cytochrome c (CytC) and caspase-3 activities in the hippocampus were also recorded. We found extensive neuronal damage in the CA3 region in the kindling group, which was preceded by increases of ROS level and MDA concentration and was followed by caspase-3 activation and an increase in cytosolic CytC. Treatment with ATX markedly attenuated the neuronal damage. In addition, ATX significantly decreased ROS and MDA concentrations and increased GSH levels. Moreover, ATX suppressed the translation of CytC release and caspase-3 activation in hippocampus. Together, these results suggest that ATX protects against neuronal loss due to epilepsy in the rat hippocampus by attenuating oxidative damage, lipid peroxidation and inhibiting the mitochondrion-related apoptotic pathway.

Topics: Animals; Caspase 3; Cytochromes c; Enzyme Activation; Hippocampus; Kindling, Neurologic; Male; Neurons; Neuroprotective Agents; Oxidative Stress; Protein Transport; Rats, Sprague-Dawley; Xanthophylls

Oxidative stress is an important molecular mechanism underlying lung fibrosis. The mitochondrion is a major organelle for oxidative stress in cells. Therefore, blocking the mitochondrial signalling pathway may be the best therapeutic manoeuver to ameliorate lung fibrosis. Astaxanthin (AST) is an excellent antioxidant, but no study has addressed the pathway of AST against pulmonary oxidative stress and free radicals by the mitochondrion-mediated signalling pathway. In this study, we investigated the antioxidative effects of AST against H2 O2 - or bleomycin (BLM)-induced mitochondrial dysfunction and reactive oxygen species (ROS) production in alveolar epithelial cells type II (AECs-II) in vivo and in vitro. Our data show that AST blocks H2 O2 - or BLM-induced ROS generation and dose-dependent apoptosis in AECs-II, as characterized by changes in cell and mitochondria morphology, translocation of apoptotic proteins, inhibition of cytochrome c (Cyt c) release, and the activation of caspase-9, caspase-3, Nrf-2 and other cytoprotective genes. These data suggest that AST inhibits apoptosis in AECs-II cells through the ROS-dependent mitochondrial signalling pathway and may be of potential therapeutic value in lung fibrosis treatment.

Topics: Antioxidants; Apoptosis; Cell Line; Cytochromes c; Epithelial Cells; Fibrosis; Free Radicals; Humans; Mitochondria; Oxidative Stress; Pulmonary Alveoli; Reactive Oxygen Species; Signal Transduction; Xanthophylls

Astaxanthin is a powerful antioxidant that occurs naturally in a wide variety of living organisms. The aim of this study is to investigate the effect and the mechanism of astaxanthin on reactive oxygen species (ROS)-mediated apoptosis in dopaminergic SH-SY5Y cells. The treatment with DHA hydroperoxide (DHA-OOH) or 6-hydroxydopamine (6-OHDA), either of which is ROS-inducing neurotoxin, led to a significant decrease in viable dopaminergic SH-SY5Y cells by MTT assay, whereas a significant protection was shown while the cells were pretreated with astaxanthin. Moreover, 100 nM astaxanthin pretreatment significantly inhibited apoptosis, mitochondrial abnormalities and intracellular ROS generation occurred in either DHA-OOH- or 6-OHDA-treated cells. The neuroprotective effect of astaxanthin is suggested to be dependent upon its antioxidant potential and mitochondria protection; therefore, it is suggested that astaxanthin may be an effective treatment for oxidative stress-associated neurodegeneration.

Topics: Antioxidants; Apoptosis; Blotting, Western; Cell Line; Cell Survival; Chromatography, High Pressure Liquid; Cytochromes c; DNA Fragmentation; Docosahexaenoic Acids; Dopamine; Humans; Lipid Peroxides; Membrane Potential, Mitochondrial; Microscopy, Fluorescence; Mitochondria; Neurons; Oxidopamine; Protein Carbonylation; Reactive Oxygen Species; Xanthophylls

Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.

Topics: Aconitate Hydratase; Animals; Behavior, Animal; Brain Injuries; Brain Ischemia; Cerebrovascular Circulation; Crustacea; Cytochromes c; Diet; Glutamic Acid; Humans; In Situ Nick-End Labeling; Lipid Peroxidation; Male; Molecular Structure; Motor Activity; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Xanthophylls

Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta. Although understanding of the pathogenesis of PD remains incomplete, increasing evidence from human and animal studies has suggested that oxidative stress is an important mediator in its pathogenesis. Astaxanthin (Asx), a potent antioxidant, has been thought to provide health benefits by decreasing the risk of oxidative stress-related diseases. This study examined the protective effects of Asx on 6-hydroxydopamine (6-OHDA)-induced apoptosis in the human neuroblastoma cell line SH-SY5Y. Pre-treatment of SH-SY5Y cells with Asx suppressed 6-OHDA-induced apoptosis in a dose-dependent manner. In addition, Asx strikingly inhibited 6-OHDA-induced mitochondrial dysfunctions, including lowered membrane potential and the cleavage of caspase 9, caspase 3, and poly(ADP-ribose) polymerase. In western blot analysis, 6-OHDA activated p38 MAPK, c-jun NH(2)-terminal kinase 1/2, and extracellular signal-regulated kinase 1/2, while Asx blocked the phosphorylation of p38 MAPK but not c-jun NH(2)-terminal kinase 1/2 and extracellular signal-regulated kinase 1/2. Pharmacological approaches showed that the activation of p38 MAPK has a critical role in 6-OHDA-induced mitochondrial dysfunctions and apoptosis. Furthermore, Asx markedly abolished 6-OHDA-induced reactive oxygen species generation, which resulted in the blockade of p38 MAPK activation and apoptosis induced by 6-OHDA treatment. Taken together, the present results indicated that the protective effects of Asx on apoptosis in SH-SY5Y cells may be, at least in part, attributable to the its potent antioxidative ability.

Topics: Adrenergic Agents; Annexin A5; Apoptosis; Caspase 3; Cell Line, Tumor; Cytochromes c; DNA Fragmentation; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Neoplastic; Humans; Membrane Potential, Mitochondrial; Neuroblastoma; Neuroprotective Agents; Oxidopamine; p38 Mitogen-Activated Protein Kinases; Reactive Oxygen Species; Xanthophylls