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Protective Effect Of MitoQ Against Dichlorvos Induced Oxidative Stress And Ensuing Dopaminergic Neuronal Cell Death
transferase (GST) and superoxide dismutase (SOD); as well as by determining the levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). Results: Results indicate that hexane extract of P. hexandrum has exhibited the good radical scavenging capacity in neutralization of DPPH, O2•−, OH• and H2O2 radicals in a dose dependent manner. Results from the study showed that n-hexane extract of Podophyllum hexandrum at the doses of (20, 30 and 50 mg/kg-day) produced hepatoprotective effect by decreasing the activity of serum marker enzymes, while it significantly increased the levels of glutathione (GSH), glutathione peroxidase (GPX), glutathione reductase (GR), super oxide dismutase (SOD) and glutathione-S-transferase (GST) in a dose dependant manner. The effect of nhexane extract was comparable to that of standard antioxidant vitamin E. doi:10.1016/j.freeradbiomed.2012.08.222
intensity of Naph-DiPy nitroxide did not enhance in response to various reductants such as glutathione and reactive oxygen species. To confirm the practical usefulness of fluorophore-nitroxide probe, we applied Naph-DiPy nitroxide for the measurement of ascorbic acid in the plasma of osteogenic disorder Shionogi (ODS) rat. Ascorbic acid level decreases in the tissues and plasma of ODS rats, when fed an ascorbic aciddeficient diet. These results suggested that the novel application of fluorophore-nitroxide probe could sensitively and easily detect ascorbic acid and be useful tools for diagnosis in disease state. Keywords: ESR, fluorescence, Nitroxide, ascorbic acid doi:10.1016/j.freeradbiomed.2012.08.223 [0489] Protective Effect Of MitoQ Against Dichlorvos Induced Oxidative Stress And Ensuing Dopaminergic Neuronal Cell Death
[0485] Rapid and convenient detection of ascorbic acid: application of fluorescent nitroxide switch M. Yamato*, Y. Matsuoka, T. Yamasaki, F. Mito, K. Yamada Kyushu University, Japan Ascorbic acid is a small molecule reductant, and has multiple functions in vivo. By reducing ascorbic acid intake, the lack of hydroxylation of prolines and lysines causes a looser triple helix, resulting in scurvy. Ascorbic acid acts as antioxidant in vivo. Ascorbic acid can scavenge superoxide anion radical, hydroxyl radical, and other radicals to prevent oxidative stress such as inflammation. Thus, rapid and convenient detection for ascorbic acid should be useful tools for diagnosis, because ascorbic acid is related to disease state. Nitroxide reduced to the corresponding hydroxylamine by ascorbic acid. Furthermore, a sensitive and novel approach, employing covalent coupling of nitroxide with a fluorophore, leads to intramolecular quenching of fluorescence emission by electron exchange interactions. Here, we show a new fluorophore-nitroxide probe with high sensitivity and selectivity for ascorbic acid, developed by utilizing the chemical properties of 2,6-substituted piperidine nitroxide. We synthesized three derivatives with various reactivates for ascorbic acid. Among them, Naph-DiPy nitroxide rapidly reacted with ascorbic acid and show fluorescence enhancement. However, fluorescence
W.Y. Wani*, A. Sunkaria, D.R. Sharma, K.D. Gill PGIMER, Chandigarh, India Introduction: Parkinson's disease (PD) is a common neurodegenerative disease characterized by loss of nigrostriatal dopamine. Evidences suggest that pesticides are one of the leading candidates of environmental toxins that may contribute to the pathogenesis of PD. We have previously shown that loss of dopamine neurons in dichlorvos exposed animals is due to oxidative damage to mitochondria in rat brains. MitoQ is an antioxidant selectively targeted to mitochondria that protects mitochondria from oxidative damage and has been shown to decrease mitochondrial damage in various animal models of oxidative stress. The present study was designed to test whether MitoQ administration has any protective effect against dichlorvos mediated oxidative stress and ensuing PC12 cell death. Methods: To assess this we investigated the effects of pretreatment of MitoQ on the ROS generation, lipid peroxidation, glutathione content, protein oxidation, and manganese superoxide dismutase (MnSOD) activity and Tyrosine Hydroxylase (TH) levels in PC12 cells treated with Dichlorvos. Results: Pretreatment of MitoQ (1µM) reduced oxidative stress (decreased ROS production and increased MnSOD activity, increased reduced glutathione content) with decreased lipid peroxidation and protein oxidation. Moreover, MitoQ pretreatment resulted in prevention of Dichlorvos induced reduction of Tyrosine hydroxylase and release of cytochrome c (cyt c) from mitochondria. Furthermore, MitoQ pretreatment also prevented the oxidative stress induced downregulation of Lon protease
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intensity of Naph-DiPy nitroxide did not enhance in response to various reductants such as glutathione and reactive oxygen species. To confirm the practical usefulness of fluorophore-nitroxide probe, we applied Naph-DiPy nitroxide for the measurement of ascorbic acid in the plasma of osteogenic disorder Shionogi (ODS) rat. Ascorbic acid level decreases in the tissues and plasma of ODS rats, when fed an ascorbic aciddeficient diet. These results suggested that the novel application of fluorophore-nitroxide probe could sensitively and easily detect ascorbic acid and be useful tools for diagnosis in disease state. Keywords: ESR, fluorescence, Nitroxide, ascorbic acid doi:10.1016/j.freeradbiomed.2012.08.223 [0489] Protective Effect Of MitoQ Against Dichlorvos Induced Oxidative Stress And Ensuing Dopaminergic Neuronal Cell Death
[0485] Rapid and convenient detection of ascorbic acid: application of fluorescent nitroxide switch M. Yamato*, Y. Matsuoka, T. Yamasaki, F. Mito, K. Yamada Kyushu University, Japan Ascorbic acid is a small molecule reductant, and has multiple functions in vivo. By reducing ascorbic acid intake, the lack of hydroxylation of prolines and lysines causes a looser triple helix, resulting in scurvy. Ascorbic acid acts as antioxidant in vivo. Ascorbic acid can scavenge superoxide anion radical, hydroxyl radical, and other radicals to prevent oxidative stress such as inflammation. Thus, rapid and convenient detection for ascorbic acid should be useful tools for diagnosis, because ascorbic acid is related to disease state. Nitroxide reduced to the corresponding hydroxylamine by ascorbic acid. Furthermore, a sensitive and novel approach, employing covalent coupling of nitroxide with a fluorophore, leads to intramolecular quenching of fluorescence emission by electron exchange interactions. Here, we show a new fluorophore-nitroxide probe with high sensitivity and selectivity for ascorbic acid, developed by utilizing the chemical properties of 2,6-substituted piperidine nitroxide. We synthesized three derivatives with various reactivates for ascorbic acid. Among them, Naph-DiPy nitroxide rapidly reacted with ascorbic acid and show fluorescence enhancement. However, fluorescence
W.Y. Wani*, A. Sunkaria, D.R. Sharma, K.D. Gill PGIMER, Chandigarh, India Introduction: Parkinson's disease (PD) is a common neurodegenerative disease characterized by loss of nigrostriatal dopamine. Evidences suggest that pesticides are one of the leading candidates of environmental toxins that may contribute to the pathogenesis of PD. We have previously shown that loss of dopamine neurons in dichlorvos exposed animals is due to oxidative damage to mitochondria in rat brains. MitoQ is an antioxidant selectively targeted to mitochondria that protects mitochondria from oxidative damage and has been shown to decrease mitochondrial damage in various animal models of oxidative stress. The present study was designed to test whether MitoQ administration has any protective effect against dichlorvos mediated oxidative stress and ensuing PC12 cell death. Methods: To assess this we investigated the effects of pretreatment of MitoQ on the ROS generation, lipid peroxidation, glutathione content, protein oxidation, and manganese superoxide dismutase (MnSOD) activity and Tyrosine Hydroxylase (TH) levels in PC12 cells treated with Dichlorvos. Results: Pretreatment of MitoQ (1µM) reduced oxidative stress (decreased ROS production and increased MnSOD activity, increased reduced glutathione content) with decreased lipid peroxidation and protein oxidation. Moreover, MitoQ pretreatment resulted in prevention of Dichlorvos induced reduction of Tyrosine hydroxylase and release of cytochrome c (cyt c) from mitochondria. Furthermore, MitoQ pretreatment also prevented the oxidative stress induced downregulation of Lon protease
S107