MnSOD Activity Research Articles

Retraction: Radenovic L. Effect of 7-nitroindazole on superoxide production and MnSOD activity in the rat brain following kainate-induced neurotoxicity. Arch biol sci, 2008, 60(1):25-32. DOI: 10.2298/ABS0801025R

This is a notice of retraction of the article: Effect of 7-nitroindazole on superoxide production and MnSOD activity in the rat brain following kainate-induced neurotoxicity, published in the Archives of Biological Sciences in 2008, Vol. 60, Issue 1. The Editor-in-Chief has been informed that this paper plagiarizes an earlier paper: Radenovic L, Selakovic V, Kartelija G, Todorovic N, Nedeljkovic M. Differential effects of NMDA and AMPA/kainate receptor antagonists on superoxide production and MnSOD activity in rat brain following intrahippocampal injection. Brain Res Bull, 2004, 64(1):85-93. The results in the article being retracted were presented as findings obtained from novel research. Inspection of the results has revealed that they were part of research already presented in the original article without appropriate justification or cross-referencing. The Editor-in-Chief considered publishing a notice of redundancy specifying the elements published previously. However, since the original article had already been autoplagiarized by the same corresponding author in the same journal (retraction DOI:10.2298/ABS150318026E), the article is being retracted in accordance with the publishing ethics of the Archives of Biological Sciences in order to preserve the integrity of scientific research. We apologize to the journal's readers that it took so long to notice this error and instigate retraction of the paper. We request our readers to contact the editorial office and editors of the journal directly should similar cases occur in the future, so that the necessary action can be taken more promptly. <br><br><font color="red"><b> Link to the retracted article <u><a href="http://dx.doi.org/10.2298/ABS0801025R">10.2298/ABS0801025R</a></b></u>

Retraction: Radenovic L, Selakovic V. Mitochondrial superoxide production and MnSOD activity following exposure to an agonist and antagonists of ionotropic receptors in rat brain, Arch Biol Sci. 2005; 57(1):1-10, DOI:10.2298/ABS0501001R

This is a notice of retraction of the article: Mitochondrial superoxide production and MnSOD activity following exposure to an agonist and antagonists of ionotropic glutamate receptors in rat brain, published in the Archives of Biological Sciences in 2005, Vol. 57, Issue 1. The Editor-in-Chief has been informed that this paper plagiarizes an earlier paper: Radenovic L, Selakovic V, Kartelija G, Todorovic N, Nedeljkovic M. Differential effects of NMDA and AMPA/kainate receptor antagonists on superoxide production and MnSOD activity in rat brain following intrahippocampal injection. Brain Res Bull, 2004, 64(1):85-93. This claim is correct and almost the entire paper is a verbatim copy of the earlier one. After confirmation of this fact, the Editor-in-Chief of the Archives of Biological Sciences has decided to retract the paper immediately. We apologize to the readers of the journal that it took so many years to notice this error and to retract the paper. We request readers of the journal to directly get in touch with the editorial office and the editors of the journal for similar cases in the future, so that they can be handled promptly. <br><br><font color="red"><b> Link to the retracted article <u><a href="http://dx.doi.org/10.2298/ABS0501001R">10.2298/ABS0501001R</a></b></u>

Retraction: Radenovic L, Selakovic V. Kainate-induced oxidative stress and neurotoxicity in the rat brain, Arch Biol Sci, 2005, 57(4):259-266, DOI: 10.2298/ABS0504259R

This is a notice of retraction of the article: Kainate-induced oxidative stress and neurotoxicity in the rat brain, published in the Archives of Biological Sciences in 2005, Vol. 57, Issue 4. The Editor-in-Chief has been informed that this paper plagiarizes an earlier paper: Radenovic L, Jovanovic M, Vasiljevic I, Selakovic V. Superoxide production and the activity of MnSOD in rat brain after intrahippocampal kainate-induced seizure. Neurosci Res Comm, 2004, 34(2):92-103. This claim is correct and almost the entire paper is a verbatim copy of the earlier one. After confirmation of this fact, the Editor-in-Chief of the Archives of Biological Sciences has decided to retract the paper immediately. We apologize to the readers of the journal that it took so many years to notice this error and to retract the paper. We request readers of the journal to directly get in touch with the editorial office and the editors of the journal for similar cases in the future, so that they can be handled promptly. <br><br><font color="red"><b> Link to the retracted article <u><a href="http://dx.doi.org/10.2298/ABS0504259R">10.2298/ABS0504259R</a></b></u>

Neuroprotective Effect of Radix Trichosanthis Saponins on Subarachnoid Hemorrhage.

Redox homeostasis has been implicated in subarachnoid hemorrhage (SAH). As a result, antioxidants and/or free radical scavengers have become an important therapeutic modality. Considering that radix trichosanthis (RT) saponins exhibited strong antioxidant ability both in vivo and in vitro, the present study aimed to reveal whether the neuroprotective activities of RT saponins were mediated by p38/p53 signal pathway after SAH. An established SAH model was used and superoxide dismutase (SOD), malondialdehyde (MDA), induced nitric oxide synthase (iNOS), nitric oxide (NO), lactate dehydrogenase (LDH), p-p38, and p53 activation were detected after 48 h of SAH. The results showed that RT saponins inhibited iNOS expression to restore NO to basal level. Moreover, compared with Cu/Zn-SOD, RT saponins (2 mg/kg/d dosage) significantly increased Mn-SOD activity after SAH. Accompanied with lowered NO and elevated SOD, decreased p38 phosphorylation and p53 activities were observed, especially for RT saponins at 2 mg/kg/d dosage. In this setting, the neurological outcome was also improved with less neuronal cells damage after RT saponins pretreatment. Our findings demonstrated the beneficial effects of RT saponins in enhancing neuroprotective effects by deducing iNOS activity, normalizing SOD level, and inhibiting p-p38 and p53 expression, hence offering significant therapeutic implications for SAH.

The influence of macro and trace elements on sperm quality

The aim of this study was to examine the association between combined concentrations of macro and trace elements and markers of oxidative stress and antioxidative defense system function together with selected cytokine levels. Based on the combined medians of the seminal plasma levels of calcium, magnesium, zinc, copper, iron, and selenium, the study subjects (88 fertile male volunteers) were divided into the following two subgroups: the Me-L group (low level of metals) and the Me-H group (high level of metals). There was a tendency toward reduced motility in the Me-H group compared to that in the Me-L group. The total protein, albumin, and total oxidation status (TOS) levels were significantly higher in the Me-H group than in the Me-L group. The total superoxide dismutase (SOD), Mn-SOD, and CuZn-SOD, activity in spermatozoa were significantly lower in the Me-H group than in the Me-L group. In seminal plasma, the Mn-SOD activity was significantly higher in the Me-H group, whereas the CuZn-SOD activity was significantly lower. Additionally, the activity levels of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were lower in the Me-H group. The medians of IL-1β, IL-10, and IL-12 were significantly higher in the Me-H group than in the Me-L group, whereas the medians of IL-2, IL-5, and IL-13 were significantly lower. Higher levels of macro and trace elements in the seminal plasma of fertile males may be associated with decreased motility. Higher levels of the examined metals are associated with elevated oxidative stress accompanied by decreased activities of some of the antioxidant enzymes and increased pro-inflammatory cytokine levels.

MicroRNA-424 protects against focal cerebral ischemia and reperfusion injury in mice by suppressing oxidative stress.

We previously showed that the microRNA miR-424 protects against permanent cerebral ischemic injury in mice by suppressing microglia activation. This study investigated the role of miR-424 in transient cerebral ischemia in mice with a focus on oxidative stress-induced neuronal injury. Transient cerebral ischemia was induced in C57/BL6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion (ischemia/reperfusion). The miR-424 level in the peri-infarct cortex was quantified. Mice were also administered miR-424 angomir by intracerebroventricular injection. Cerebral infarct volume, neuronal apoptosis, and levels of oxidative stress markers and antioxidants were evaluated. In an in vitro experiment, primary cortical neurons were exposed to H2O2 and treated with miR-424 angomir, nuclear factor erythroid 2-related factor 2 siRNA, and superoxide dismutase (SOD) inhibitor; cell activity, lactate dehydrogenase release, malondialdehyde level, and manganese (Mn)SOD activity were then evaluated. MiR-424 levels in the peri-infarct cortex increased at 1 and 4 hours then decreased 24 hours after reperfusion. Treatment with miR-424 decreased infarct volume and inhibited neuronal apoptosis after ischemia/reperfusion, reduced reactive oxygen species and malondialdehyde levels in the cortex, and increased the expression and activation of MnSOD as well as the expression of extracellular SOD and the redox-sensitive transcription factor nuclear factor erythroid 2-related factor. In neuronal cultures, miR-424 treatment abrogated H2O2-induced injury, as evidenced by decreased lactate dehydrogenase leakage and malondialdehyde level and increased cell viability and MnSOD activity; the protective effects of miR-424 against oxidative stress were reversed by nuclear factor erythroid 2-related factor knockdown and SOD inhibitor treatment. MiR-424 protects against transient cerebral ischemia/reperfusion injury by inhibiting oxidative stress.

Protective effect of Mn(III)-desferrioxamine B upon oxidative stress caused by ozone and acid rain in the Brazilian soybean cultivar Glycine max "Sambaiba".

This study aimed to investigate the effects of the Mn complex (Mn(III)-desferrioxamine B (MnDFB)) on oxidative stress in the Brazilian soybean cultivar Glycine max "Sambaiba" following exposure to ozone and acid rain. We determined the suitable dose of MnDFB to apply to G. max seedlings using a dose-response curve. The highest superoxide dismutase (SOD) activity and Mn content in leaves were found upon the application of 8μM MnDFB. Thus, G. max seedlings pretreated with 8μM MnDFB were individually exposed to ozone and acid rain simulated. Pretreatment with MnDFB reduced lipid peroxidation upon ozone exposure and increased SOD activity in leaves; it did not alter the metal content in any part of the plant. Conversely, following acid rain exposure, neither the metal content in leaves nor SOD enzyme activity were directly affected by MnDFB, unlike pH. Our findings demonstrated that exogenous MnDFB application before ozone exposure may modulate the MnSOD, Cu/ZnSOD, and FeSOD activities to combat the ROS excess in the cell. Here, we demonstrated that the applied dose of MnDFB enhances antioxidative defenses in soybean following exposure to acid rain and especially to ozone.

Histidine-tryptophan-ketoglutarate solution with added ebselen augments myocardial protection in neonatal porcine hearts undergoing ischemia/reperfusion.

Whether modified histidine-tryptophan-ketoglutarate (HTK) solution offers myocardial protection to newborn heart has not been documented. The purpose of this study was to compare myocardial protection using HTK added by ebselen with HTK in a piglet model of cardiopulmonary bypass (CPB). Fifteen piglets were randomly assigned to three groups: the control group (C group, n = 5), HTK solution group (HTK group, n = 5), and HTK added by 10 nM ebselen group (HTK+E group, n = 5). Animals in the two experimental groups were placed on hypothermic CPB, after which the ascending aorta had been clamped for 2 h. The control animals underwent normothermic CPB without cardiac arrest. Myocardial antioxidant activities, myocytes apoptosis and mitochondrial structures, as well as the release of cytochrome c and the expression of Bax, Bcl-2, and HSP72 protein in myocardium were measured. Increased myocardial superoxide dismutase (SOD) and Mn-SOD activities, decreased TUNEL-positive cells, and reduced release of cytochrome c were noted in the HTK+E group compared with those in the HTK group (P = 0.021, P = 0.020, P = 0.045, and P = 0.010, respectively). The Bax/Bcl-2 ratio in the HTK group was significantly higher than that in the C group (P = 0.024). The expression of HSP72 protein and mRNA in the HTK+E group was higher than that in the HTK group (P = 0.039 and P = 0.035, respectively). Mitochondrial score under electron microscope in the HTK+E group was lower than that in the HTK group (P = 0.047). Improved antioxidant defense, reduced myocytes apoptosis, and better preserved mitochondrial structure were observed in the HTK+E group. Ebselen added to HTK provides better myocardioprotection to HTK solution for the neonatal heart.

Activity of different subtypes of superoxide dismutase in acute period of ischemic stroke

86 patients in the acute period of ischemic stroke (IS) were involved in a study of the activity of general SOD, intracellular (Cu,Zn-SOD), mitochondrial (Mn-SOD2) and numbers of white blood cells with a high content of intracellular reactive oxygen species (ROS+-cells). A reduction of activity of general SOD, Cu,Zn-СОД, Mn-SOD and increase of ROS+-cells number were detected. There was a reliable negative correlation between activity of general SOD, Mn-SOD and the number of ROS+-cells on the 1st day of IS. It was established that the activity of the general SOD, Cu,Zn-СОД, Mn-SOD and number of ROS+-cells depend on the severity of the IS and the infarct size. Credible negative correlations were found at the moderate and severe IS and infarct size 10-100 cm2. A direct reliable correlation between the content of ROS+-cells and degree of the severity and size of the IS were observed.

Mycorrhizal-induced calmodulin mediated changes in antioxidant enzymes and growth response of drought-stressed trifoliate orange.

Trifoliate orange [Poncirus trifoliata (L) Raf.] is considered highly arbuscular mycorrhizal (AM) dependent for growth responses through a series of signal transductions in form of various physiological responses. The proposed study was carried out to evaluate the effect of an AM fungus (Funneliformis mosseae) on growth, antioxidant enzyme (catalase, CAT; superoxide dismutase, SOD) activities, leaf relative water content (RWC), calmodulin (CaM), superoxide anion (), and hydrogen peroxide (H2O2) concentrations in leaves of the plants exposed to both well-watered (WW) and drought stress (DS) conditions. A 58-day of DS significantly decreased mycorrhizal colonization by 60% than WW. Compared to non-AM seedlings, AM seedlings displayed significantly higher shoot morphological properties (plant height, stem diameter, and leaf number), biomass production (shoot and root fresh weight) and leaf RWC, regardless of soil water status. AM inoculation significantly increased CaM and soluble protein concentrations and CAT activity, whereas significantly decreased and H2O2 concentration under both WW and DS conditions. The AM seedlings also exhibited significantly higher Cu/Zn-SOD and Mn-SOD activities than the non-AM seedlings under DS but not under WW, which are triggered by higher CaM levels in AM plants on the basis of correlation studies. Further, the negative correlation of Cu/Zn-SOD and Mn-SOD activities with and H2O2 concentration showed the DS-induced ROS scavenging ability of CaM mediated SODs under mycorrhization. Our results demonstrated that AM-inoculation elevated the synthesis of CaM in leaves and up-regulated activities of the antioxidant enzymes, thereby, repairing the possible oxidative damage to plants by lowering the ROS accumulation under DS condition.

Estrogen plus progestin increase superoxide dismutase and total antioxidant capacity in postmenopausal women

Objective This cross-sectional study aimed to evaluate the behavior of blood antioxidant enzymes (superoxide dismutase (SOD), catalase and glutathione peroxidase), plasma total antioxidant capacity and oxidative damage (lipid oxidation and protein carbonyl levels) and their relationship with the serum levels of steroid hormones in premenopausal and postmenopausal women without and with estrogen alone (ET) or estrogen plus progestin therapy (EPT).Methods Blood was collected from four groups of subjects: premenopausal women (n = 24), postmenopausal women without hormone therapy (n = 31), postmenopausal women with ET (n = 12) and postmenopausal women with EPT (n = 16).Results The activities of the different SOD isoforms (CuZnSOD and MnSOD) and the plasma total antioxidant power were significantly higher in the postmenopausal women under EPT than in the postmenopausal women without hormone replacement therapy (HRT). Only CuZnSOD activity was increased in women receiving ET compared to the postmenopausal women without HRT. However, no differences were observed in the levels of lipid or protein oxidation or in the non-enzymatic plasma antioxidants (uric acid and albumin) among the groups. The duration of HRT and serum estrogen levels were positively correlated to the blood CuZnSOD activity and to plasma total antioxidant power, whereas the serum progesterone levels were positively correlated to CuZnSOD activity and negatively correlated to protein carbonyl groups. Interestingly, the total antioxidant power of plasma was positively correlated to CuZnSOD and glutathione peroxidase activities.Conclusion We conclude that EPT increases blood MnSOD and CuZnSOD activity in postmenopausal women, leading to an increased plasma total antioxidant capacity. This finding may be relevant to the prevention of oxidative stress-related disorders in postmenopausal women.

Physical exercise prior and during treatment reduces sub-chronic doxorubicin-induced mitochondrial toxicity and oxidative stress

Doxorubicin (DOX) is an anti-cancer agent whose clinical usage results in a cumulative and dose-dependent cardiotoxicity. We have previously shown that exercise performed prior to DOX treatment reduces the resulting cardiac(mito) toxicity. We sought to determine the effects on cardiac mitochondrial toxicity of two distinct chronic exercise models (endurance treadmill training—TM and voluntary free-wheel activity—FW) when used prior and during DOX treatment.Male-young Sprague–Dawley rats were divided into six groups (n=6 per group): SAL+SED (saline sedentary), SAL+TM (12-weeks TM), SAL+FW (12-weeks FW), DOX+SED (7-weeks of chronic DOX treatment 2mg/kg per week), DOX+TM and DOX+FW. DOX administration started 5weeks after the beginning of the exercise protocol. Heart mitochondrial ultrastructural alterations, mitochondrial function (oxygen consumption and membrane potential), semi-quantification of oxidative phosphorylation (OXPHOS) proteins and their in-gel activity, as well as proteins involved in mitochondrial oxidative stress (SIRT3, p66shc and UCP2), biogenesis (PGC1α and TFAM), acetylation and markers for oxidative damage (carbonyl groups, MDA,SH, aconitase, Mn-SOD activity) were evaluated. DOX treatment resulted in ultrastructural and functional alterations and decreased OXPHOS. Moreover, DOX decreased complex I activity and content, mitochondrial biogenesis (TFAM), increased acetylation and oxidative stress. TM and FW prevented DOX-induced alteration in OXPHOS, the increase in oxidative stress, the decrease in complex V activity and in complex I activity and content. DOX-induced decreases in TFAM and SIRT3 content were prevented by TM only.Both chronic models of physical exercise performed before and during the course of sub-chronic DOX treatment translated into an improved mitochondrial bioenergetic fitness, which may result in part from the prevention of mitochondrial oxidative stress and damage.

Comparative study on the effects of chelated or inorganic manganese in diets containing tricalcium phosphate and phytate on the growth performance and physiological responses of turbot Scophthalmus maximus

A growth trial was conducted to evaluate the effects of chelated (Mintrex™ Mn, Mn-M) or inorganic (MnSO4·H2O, Mn-S) manganese (Mn) on growth, feed utilization, tissue Mn deposition and liver superoxide dismutase (SOD) activity in turbot Scophthalmus maximus. A semi-purified basal diet was formulated to be deficient in Mn (3.7 mg kg−1) and contained tricalcium phosphate and sodium phytate at levels of 20 and 5 g kg−1, respectively. Ten other diets were made by adding five levels (5, 10, 20, 35 and 55 mg Mn kg−1 diet) of either the Mn-M or Mn-S to the basal diet, respectively. The 11 experimental diets were fed to groups of turbot (mean initial weight: 4.6 g) for 8 weeks. Results showed that the specific growth rate (SGR), feed intake, whole body Mn/vertebra Mn concentration and Mn-SOD activity in liver were significantly improved by Mn supplementation (P 0.05).

Effects of antioxidant gene therapy on the development of diabetic retinopathy and the metabolic memory phenomenon.

The purpose of this study was to determine the therapeutic effect and mechanism of AAV-MnSOD by intravitreal injection on diabetic retinopathy (DRP) and the metabolic memory phenomenon. The effect of hyperglycemia and metabolic memory on the thickness of basement membrane, ratio of pericyte area and cross-sectional area of capillary vessels in the nerve fiber layer and outer plexiform layer; retinal capillary cell apoptosis; number of acellular capillaries and activities of retinal MnSOD and catalase were examined and compared with intravitreal injection of AAV-MnSOD by transmission electron microscopy, TUNEL assay, ELISA, and immunohistochemistry. Hyperglycemia increased the thickness of capillary basement membranes in the nerve fiber layer and outer plexiform layer, decreased the ratio of pericyte area and cross-sectional area of capillary vessels, increased numbers of acellular capillaries and apoptosis of retinal capillary cells, and decreased activities of retinal MnSOD and catalase. Termination of hyperglycemia cannot reverse pathological changes listed above. Intra-vitreal injection of AAV-MnSOD dramatically elevated the level and activities of retinal MnSOD and catalase, and effectively prevented the progression of DRP and the metabolic memory phenomenon. Increasing reactive oxygen species concentration and continuous decreasing of antioxidant enzyme activity play important roles in DRP and the metabolic memory phenomenon. AAV-MnSOD gene therapy provides a promising strategy to inhibit this blinding disease.

Effects of dietary manganese sources and levels on growth performance, relative manganese bioavailability, antioxidant activities and tissue mineral content of juvenile cobia (Rachycentron canadumL)

This study was conducted to compare the effects of manganese sulphate (Mn-S), glycine manganese(Mn-Gly) and manganese 2-hydroxy-4-(methylthio)butyrate (Mn-HMB) on juvenile cobia, Rachycentron canadum L. Treatments consisted of 0, 2, 4, 8, 16 or 32 mg supplemental Mn kg−1 from Mn-S, Mn-Gly or Mn-MHB. Growth performance, manganese status, antioxidant activities and tissue mineral content were analysed after a 70-day feeding period. Specific growth rate (SGR) increased with feeding 6.29 to 12.65 mg Mn kg−1 diet from the Mn-S or 6.86 to 12.39 mg Mn kg−1 from the Mn-Gly or 6.50 to 8.33 mg Mn kg−1 from the Mn-HMB and then plateaued above these levels. Feed conversion ratio (FCR) show decreasing first and then increased trend. Survival rate (SR) were not affected by the dietary treatments (P > 0.05). Fish fed diets supplemented with manganese at levels of 4–32 mg Mn kg−1 had obviously higher hepatic Mn-SOD activity (P < 0.05); on the contrary, hepatic has lower malondialdehyde (MDA) content (P < 0.05) than fish fed the basal diet. The manganese concentrations of whole body and vertebrae increased with increasing dietary Mn levels from 2–32 mg Mn kg−1 (independent on manganese sources). Dietary Mn supplementation did not significantly influence the copper concentrations of whole body and vertebrae, the zinc concentrations of whole body and liver. Analysis by the broken-line regression of SGR indicated that the optimal dietary Mn requirements in juvenile cobia were 15.42, 11.22 and 10.50 mg Mn kg−1 diet from Mn-S, Mn-Gly or Mn-HMB respectively.

Effects of static magnetic field pretreatment with and without PEG 6000 or NaCl exposure on wheat biochemical parameters

In this study, the static magnetic field (SMF) flux of 2.9–4.7 mT was applied to mature embryo explants of Tekirdag and Selimiye wheat cultivars (Triticum aestivum L.) under tissue culture conditions at three different pretreatment times of 0, 2.2, and 19.8 s, at the rate of 1 m/s with and without 60 g/L PEG 6000 or 100 mM NaCl. Changes in different biochemical parameters were investigated. SMF pretreatment with and without 60 g/L PEG 6000 or 100 mM NaCl increased chlorophyll and carotenoid contents, FRAP values, and antioxidant enzyme (SOD, CAT, POX, and APX) activities in all experimental groups except for the activities of Mn-SOD in the cv. Selimiye root samples. Among SOD isozymes, Fe-SOD was affected by SMF stronger than other izozymes. The combinations of SMF pretreatment with and without 60 g/L PEG 6000 or 100 mM NaCl differently affected SOD isozyme activities besides its effects on other biochemical parameters.

Antimutagenic and antigenotoxic potential of grape juice concentrate in blood and liver of rats exposed to cadmium.

The aim of this study was to evaluate the antimutagenic and antigenotoxic potential of grape juice concentrate in rodent organs exposed to cadmium chloride intoxication. A total of 15 Wistar rats were distributed into three groups (n = 5), as follows: control group (CTRL; nontreated group), cadmium group (Cd), and cadmium-grape juice group (Cd + GJ). Exposed animals received intraperitoneal injection of cadmium chloride (1.2 mg/kg body weight) diluted in water and, after 15 days, Cd + GJ group received grape juice concentrate for 15 days, by gavage (0.8 mL, 1.18 mg of polyphenols kg(-1) day(-1)). Grape juice concentrate was able to decrease genotoxic effects induced by cadmium in peripheral blood and liver cells as depicted by single cell gel (comet) and micronucleus assays. A decrease for anti-8-hydroxy-20-deoxyguanosine (8OHdG) expression in hepatocytes of animals exposed to cadmium and treated with grape juice concentrate was also detected. Higher CuZn-SOD activity was observed in liver cells of the Cd + GJ group. No remarkable differences were seen regarding Mn-SOD activity among groups. Taken together, our results demonstrate that grape juice concentrate was able to exert antimutagenic and antigenotoxic activities in blood and liver cells of rats exposed to cadmium.

Cytoprotective Effect of Eckol Against Oxidative Stress‐Induced Mitochondrial Dysfunction: Involvement of the FoxO3a/AMPK Pathway

This study investigated the cytoprotective effect of Ecklonia cava-derived eckol against H2O2-induced mitochondrial dysfunction in Chang liver cells. While H2O2 augmented levels of mitochondrial reactive oxygen species (ROS), eckol decreased it. Eckol also attenuated high intracellular Ca(2+) levels stimulated by H2O2 and recovered H2O2-diminished ATP levels and succinate dehydrogenase activity. Eckol time-dependently increased the expression of manganese superoxide dismutase (Mn SOD), a mitochondrial antioxidant enzyme with cytoprotective effect against oxidative stress. Eckol recovered Mn SOD expression and activity that were decreased by H2O2. Finally, eckol induced Mn SOD through phosphorylated AMP-activated protein kinase (AMPK) and forkhead box O3a (FoxO3a). Specific silencing RNAs (siRNAs) against FoxO3a and AMPK reduced eckol-stimulated Mn SOD expression, and diethyldithiocarbamate (Mn SOD inhibitor) and siRNA against Mn SOD reduced the cytoprotective effect of eckol against H2O2-provoked cell death. These results demonstrate that eckol protects cells from mitochondrial oxidative stress by activating AMPK/FoxO3a-mediated induction of Mn SOD.

L-Selenomethionine Does Not Protect Against Testosterone Plus 17β-Estradiol-Induced Oxidative Stress and Preneoplastic Lesions in the Prostate of NBL Rats

Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did not show preventive benefit, including 1 study in a rat model involving testosterone (T) and estradiol (E2)-induced prostatic oxidative stress. Here, we examined modulation of T + E2-induced prostatic oxidative stress, dysplasia, and inflammation by L-selenomethionine at 1.5 or 3.0 mg selenium/kg in NIH-07 diet in Noble (Nbl)/Crl rats treated with T + E2 for 16 wk. Hormone treatment increased immunohistochemical staining for 8-hydroxydeoxyguanosine (8-OHdG) in the prostatic sites of T + E2-induced preneoplasia (P < 0.05), but selenomethionine did not attenuate 8-OHdG staining and dysplasia in the lateral prostate. Glutathione-peroxidase activity (P < 0.05) and mRNA expression were induced by T + E2 (P < 0.0001) but not changed by selenomethionine. Selenomethionine did not cause significant responses in expression and activity of glutathione-peroxidase and MnSOD, except for a reduction of MnSOD protein expression in the lateral prostate (P < 0.01). The absence of reduction of oxidative stress and dysplasia and the minimal effects on antioxidant enzymes caused by selenomethionine are consistent with the null effects observed in selenium supplementation animal studies and clinical trials. Significant (P < 0.01) opposite apoptosis/cell proliferation balance responses to selenomethionine and to T + E2 occurred in the lateral and dorsal prostate, explaining why T + E2 induces lesions selectively in the lateral lobe of NBL rats.

Ferroportin deficiency impairs manganese metabolism in flatiron mice (995.1)

Mn homeostasis must guard against neurotoxic effects of excess metal while providing a sufficient source for growth and development. Mn is absorbed from the diet by the intestine, while excess metal is excreted into bile by the liver. In vitro evidence suggests that ferroportin (Fpn), a known Fe exporter, can also export Mn. Here we examine the physiological role for Fpn in Mn metabolism using flatiron mice, a genetic model of Fpn deficiency. Flatiron mice harbor a missense mutation (H32R) affecting Fpn localization and iron export activity. These mice fully recapitulate the human iron loading disorder “ferroportin disease”. Compared to littermate wild‐type controls, Mn levels in flatiron mice are reduced in liver by 10% and in blood by 13% (P &lt; 0.05). Using MnSOD activity as a biomarker, Mn deficiency appears as early as 6 weeks of age in flatiron mice. Pharmacokinetic studies show that intestinal 54Mn absorption is reduced in flatiron mice by 60% (P &lt; 0.05). The sum of evidence indicates that Mn deficiency develops in flatiron mice due to reduced intestinal absorption implicating a role for Fpn in this process. Notably, flatiron mice also have 51% less Mn in bile compared to controls (P &lt; 0.05). These data suggest that Fpn plays a key role in Mn homeostasis.Grant Funding Source: Research supported by NIH R01ES014638.