Glutathione (GSH), a major cellular antioxidant protects cells against oxidative stress injury. Nuclear factor erythroid 2-related factor 2 (NFE2L2/Nrf2) is a redox sensitive master regulator of battery of antioxidant...Glutathione (GSH), a major cellular antioxidant protects cells against oxidative stress injury. Nuclear factor erythroid 2-related factor 2 (NFE2L2/Nrf2) is a redox sensitive master regulator of battery of antioxidant enzymes including those involved in GSH antioxidant machinery. Earlier we reported that ethanol (ETOH) elicits apoptotic death of pri-mary cortical neurons (PCNs) which in partly due to depletion of intracellular GSH levels. Further a recent report from our laboratory illustrated that ETOH exacerbated the dysregulation of GSH and caspase mediated cell death of pure cortical neurons that are compromised in Nrf2 machinery (Narasimhan et al., 2011). In various experimental models of neurodegeneration, neuronal antioxidant defenses mainly GSH has been shown to be supported by astrocytes. We therefore sought to determine whether astrocytes can render protection to neurons against ETOH toxicity, particularly when the function of Nrf2 is compromised in neurons. The experimental model consisted of co-culturing PCAs with Nrf2 downregulated PCNs that were exposed with and without 4 mg/mL ETOH for 24 h. Monochlorobimane (MCB) staining followed by FACS analysis showed that astrocytes blocked ETOH induced GSH decrement in Nrf2-silenced neurons as opposed to exaggerated GSH depletion in Nrf2 downregulated PCNs alone. Similarly, the heightened activa-tion of caspase 3/7 observed in Nrf2-compromised neurons was attenuated when co-cultured with astrocytes as meas-ured by luminescence based caspase Glo assay. Furthermore, annexin-V-FITC staining followed by FACS analysis re-vealed that Nrf2 depleted neurons showed resistance to ETOH induced neuronal apoptosis when co-cultured with as-trocytes. Thus, the current study identifies ETOH induced dysregulation of GSH and associated apoptotic events ob-served in Nrf2-depleted neurons can be blocked by astrocytes. Further our results suggest that this neuroprotective ef-fect of astrocyte despite dysfunctional Nrf2 system in neurons could be compensated by astrocytic GSH supply.展开更多
Objective To observe the effects of chronic emotional stress on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malonialdehyde (MDA) level in female rats’ brain. Methods The rats ...Objective To observe the effects of chronic emotional stress on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malonialdehyde (MDA) level in female rats’ brain. Methods The rats were randomly divided into 4 groups: normal control group (group N), emotional stress group (group E), emotional stress + pregnancy group (group E+P) and regularly drinking group (group R). Emotional stress in rats was induced by training rats with empty drinking bottles. Having been finished the stress procedure, the brain was taken out and homogenized. Then the activities of SOD, GSH-Px and MDA level were measured. Results Compared to group N, both the activities of SOD in brain tissues of group E and group E+P were significantly decreased ( P <0.05 and P <0.01, respectively) while the MDA level increased ( P <0.05). However, the extent of changes in group E+P was more obvious than that in E. GSH-Px activities in E+P and E were significantly changed. However, the GSH-Px activity in E+P was decreased ( P <0.05) while the activity in E increased ( P <0.05).Conclusion The chronic emotional stress can reduce the antioxidative system by decreasing the antioxidative enzyme activity and potentiating the lipid peroxidation in the brain. It is also suggested that the combination of emotional stress and pregnancy can augment the oxidative damage in rats’ brain.展开更多
Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）-induced cataract.Methods:Lens from adult Sprague-Dawley...Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）-induced cataract.Methods:Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H<sub>2</sub>O<sub>2</sub>,0.2 mM of H<sub>2</sub>O<sub>2</sub> plus 0.5 mM.1.0 mM.or 2.0 mM of LA for 24 h.Cataract was assessed using cross line grey scale measurement.Superoxide dismutase（SOD）.glutathione（GSH-Px）.lactate dehydrogenase（LDH）. and maloudialdehyde（MDA）activity or level in lens homogenates was measured.Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling（TUNEL） Assay.Results:A total of 0.2 mM of H<sub>2</sub>O<sub>2</sub> induced obvious cataract formation and apoptosis in lens’ epithelial cells,but 0.5-2.0 mM of LA could block the effect of 0.2 mM H<sub>2</sub>O<sub>2</sub> in inducing cataract and apoptosis.Furthermore.0.2 mM ol H<sub>2</sub>O<sub>2</sub> significantly decreased SOD.GSH-Px,and LDH activity and significant increased MDA level in the lens,but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H<sub>2</sub>O<sub>2</sub>.One mM of LA was found to be the most effective. Conclusions:LA can protect lens from H<sub>2</sub>O<sub>2</sub>-induced cataract.LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.展开更多
Objective To investigate whether cadmium-induced oxidative stress in the kidney isinfluenced by zinc and selenium. Methods Five groups of rats were maintained: (A) Cd (CdCl2,400 mg·kg-1·day-1 intraperi...Objective To investigate whether cadmium-induced oxidative stress in the kidney isinfluenced by zinc and selenium. Methods Five groups of rats were maintained: (A) Cd (CdCl2,400 mg·kg-1·day-1 intraperitoneal injection); (B) Cd+Zn (ZnCl2, 20mg. kg-1·day-1 hypodermicinjection); (C) Cd+Se (Na2SeO3, 350 mg·kg-1·day-1 via a stomach tube); (D) Cd+Zn+Se; (E)treated with physiological saline as a sham-handled control. The rats were given treatmentfor a period of 4 weeks. The activities of superoxide dismutase (SOD), glutathione peroxidase(GH-Px), catalase (CAT), and the level of malondialdehyde (MDA) in the kidney tissue weremeasured to assess the oxidative stress. Urinary lactate dehydrogenase (LDH) activity wasused as an indicator of tubular cell damage caused by lipid peroxidation. Results In groupC and D, activities of SOD (110.5±5.2, 126.8±7.0; P < 0.05) and GSH-Px (85.7±4.9,94.6±7.3; P < 0. 05) were higher than those in group A(84.7±3.3; 56.9±3.8); and in groupB, only the activity of GSH-Px (80.0±4.3, P < 0.01) increased in comparison with that ingroup A (56.9±3.8). Significant increase of MDA (P < 0.05) was seen in group B (31.1±4.7) andC (35.0±4.1) when compared with control values (17.2±1.8). No difference was found inthe level of MDA between group D (18.9±2.6) and control. The activity of LDH in urineof control group (0.06±0.02) was lower than that of group A (0.46±0.19, P<0.05), B (0.10±0.05, P<0.05) and C (0.14±0.07, P<0.05), and there was no significant change betweencontrol (0.06±0.02) and group D (0.08±0.02). Conclusion Zinc or selenium couldpartially alleviate the oxidative stress induced by cadmium in kidney, but administrationcadmium in combination with zinc and selenium efficiently protects kidney from cadmium-induced oxidative damage.展开更多
文摘Glutathione (GSH), a major cellular antioxidant protects cells against oxidative stress injury. Nuclear factor erythroid 2-related factor 2 (NFE2L2/Nrf2) is a redox sensitive master regulator of battery of antioxidant enzymes including those involved in GSH antioxidant machinery. Earlier we reported that ethanol (ETOH) elicits apoptotic death of pri-mary cortical neurons (PCNs) which in partly due to depletion of intracellular GSH levels. Further a recent report from our laboratory illustrated that ETOH exacerbated the dysregulation of GSH and caspase mediated cell death of pure cortical neurons that are compromised in Nrf2 machinery (Narasimhan et al., 2011). In various experimental models of neurodegeneration, neuronal antioxidant defenses mainly GSH has been shown to be supported by astrocytes. We therefore sought to determine whether astrocytes can render protection to neurons against ETOH toxicity, particularly when the function of Nrf2 is compromised in neurons. The experimental model consisted of co-culturing PCAs with Nrf2 downregulated PCNs that were exposed with and without 4 mg/mL ETOH for 24 h. Monochlorobimane (MCB) staining followed by FACS analysis showed that astrocytes blocked ETOH induced GSH decrement in Nrf2-silenced neurons as opposed to exaggerated GSH depletion in Nrf2 downregulated PCNs alone. Similarly, the heightened activa-tion of caspase 3/7 observed in Nrf2-compromised neurons was attenuated when co-cultured with astrocytes as meas-ured by luminescence based caspase Glo assay. Furthermore, annexin-V-FITC staining followed by FACS analysis re-vealed that Nrf2 depleted neurons showed resistance to ETOH induced neuronal apoptosis when co-cultured with as-trocytes. Thus, the current study identifies ETOH induced dysregulation of GSH and associated apoptotic events ob-served in Nrf2-depleted neurons can be blocked by astrocytes. Further our results suggest that this neuroprotective ef-fect of astrocyte despite dysfunctional Nrf2 system in neurons could be compensated by astrocytic GSH supply.
文摘Objective To observe the effects of chronic emotional stress on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malonialdehyde (MDA) level in female rats’ brain. Methods The rats were randomly divided into 4 groups: normal control group (group N), emotional stress group (group E), emotional stress + pregnancy group (group E+P) and regularly drinking group (group R). Emotional stress in rats was induced by training rats with empty drinking bottles. Having been finished the stress procedure, the brain was taken out and homogenized. Then the activities of SOD, GSH-Px and MDA level were measured. Results Compared to group N, both the activities of SOD in brain tissues of group E and group E+P were significantly decreased ( P <0.05 and P <0.01, respectively) while the MDA level increased ( P <0.05). However, the extent of changes in group E+P was more obvious than that in E. GSH-Px activities in E+P and E were significantly changed. However, the GSH-Px activity in E+P was decreased ( P <0.05) while the activity in E increased ( P <0.05).Conclusion The chronic emotional stress can reduce the antioxidative system by decreasing the antioxidative enzyme activity and potentiating the lipid peroxidation in the brain. It is also suggested that the combination of emotional stress and pregnancy can augment the oxidative damage in rats’ brain.
文摘Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）-induced cataract.Methods:Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H<sub>2</sub>O<sub>2</sub>,0.2 mM of H<sub>2</sub>O<sub>2</sub> plus 0.5 mM.1.0 mM.or 2.0 mM of LA for 24 h.Cataract was assessed using cross line grey scale measurement.Superoxide dismutase（SOD）.glutathione（GSH-Px）.lactate dehydrogenase（LDH）. and maloudialdehyde（MDA）activity or level in lens homogenates was measured.Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling（TUNEL） Assay.Results:A total of 0.2 mM of H<sub>2</sub>O<sub>2</sub> induced obvious cataract formation and apoptosis in lens’ epithelial cells,but 0.5-2.0 mM of LA could block the effect of 0.2 mM H<sub>2</sub>O<sub>2</sub> in inducing cataract and apoptosis.Furthermore.0.2 mM ol H<sub>2</sub>O<sub>2</sub> significantly decreased SOD.GSH-Px,and LDH activity and significant increased MDA level in the lens,but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H<sub>2</sub>O<sub>2</sub>.One mM of LA was found to be the most effective. Conclusions:LA can protect lens from H<sub>2</sub>O<sub>2</sub>-induced cataract.LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.
文摘Objective To investigate whether cadmium-induced oxidative stress in the kidney isinfluenced by zinc and selenium. Methods Five groups of rats were maintained: (A) Cd (CdCl2,400 mg·kg-1·day-1 intraperitoneal injection); (B) Cd+Zn (ZnCl2, 20mg. kg-1·day-1 hypodermicinjection); (C) Cd+Se (Na2SeO3, 350 mg·kg-1·day-1 via a stomach tube); (D) Cd+Zn+Se; (E)treated with physiological saline as a sham-handled control. The rats were given treatmentfor a period of 4 weeks. The activities of superoxide dismutase (SOD), glutathione peroxidase(GH-Px), catalase (CAT), and the level of malondialdehyde (MDA) in the kidney tissue weremeasured to assess the oxidative stress. Urinary lactate dehydrogenase (LDH) activity wasused as an indicator of tubular cell damage caused by lipid peroxidation. Results In groupC and D, activities of SOD (110.5±5.2, 126.8±7.0; P < 0.05) and GSH-Px (85.7±4.9,94.6±7.3; P < 0. 05) were higher than those in group A(84.7±3.3; 56.9±3.8); and in groupB, only the activity of GSH-Px (80.0±4.3, P < 0.01) increased in comparison with that ingroup A (56.9±3.8). Significant increase of MDA (P < 0.05) was seen in group B (31.1±4.7) andC (35.0±4.1) when compared with control values (17.2±1.8). No difference was found inthe level of MDA between group D (18.9±2.6) and control. The activity of LDH in urineof control group (0.06±0.02) was lower than that of group A (0.46±0.19, P<0.05), B (0.10±0.05, P<0.05) and C (0.14±0.07, P<0.05), and there was no significant change betweencontrol (0.06±0.02) and group D (0.08±0.02). Conclusion Zinc or selenium couldpartially alleviate the oxidative stress induced by cadmium in kidney, but administrationcadmium in combination with zinc and selenium efficiently protects kidney from cadmium-induced oxidative damage.
