Zinc-containing Superoxide Dismutase Research Articles

The Effect of Sodium Alginate-Coated Nano-Zinc Oxide on the Growth Performance, Serum Indexes and Fecal Microbial Structure of Weaned Piglets.

High dose of zinc oxide (ZnO) could improve growth performance and alleviate disease status, whereas it caused serious environmental pollution and bacterial resistance. This study was to investigate whether low doses of sodium alginate-coated nano zinc oxide (saZnO), a new type of zinc resource, could serve as a potential alternative to pharmacological doses of traditional ZnO in weaned piglets. A total of 144 crossbred piglets were randomly allocated into three groups, including a basal diet without the addition of Zn (CON), a basal diet with 1600 mg Zn/kg from traditional ZnO (ZnO), and a basal diet with 500 mg Zn/kg from saZnO (saZnO). The experiment lasted for 28 days. The results showed that supplementing with ZnO and saZnO for 14 and 28 days significantly improved body weight (BW) and average daily gain (ADG) (p < 0.01) and markedly reduced the feed intake-to-gain ratio (F/G) (p < 0.05) and diarrhea rate. In addition, dietary ZnO and saZnO significantly increased the activities of the total antioxidant capacity (T-AOC) and alkaline phosphatase (ALP) (p < 0.01). Supplementing with saZnO also promoted the levels of superoxide dismutase (SOD), IgM and copper- and zinc-containing superoxide dismutase (Cu/Zn-SOD) in serum (p < 0.05), whereas a ZnO addition decreased the concentration of malondialdehyde (MDA) (p < 0.05), indicating the beneficial effect of Zn on antioxidant and immune functions. Piglets fed the ZnO diet showed higher serum Zn accumulations than those fed the CON and saZnO diets at d 28 (p < 0.01), and supplementing with ZnO and saZnO markedly contributed to Zn excretion in feces, especially in the ZnO diet (p < 0.01). Additionally, piglets fed the saZnO diet had greater valeric acid concentrations (p < 0.05) in their feces, while other short chain fatty acids (SCFAs) were not affected by different treatments (p > 0.05). Microbial alpha diversity was reduced in the saZnO group compared with the CON group (p < 0.05), while an obvious separation of microbial composition, the marker of beta diversity, was shown among the three groups (p < 0.05). At the genus level, six genera, including Clostridium_sensu_stricto_1, Terrisporobacter, f_Muribaculaceae, Subdoligranulum and Intestinibacter, were pronouncedly increased in the ZnO and saZnO groups (p < 0.05); another nine species were dramatically downregulated, such as f_Lachnospiraceae, f_Prevotellaceae, f_Butyricicoccaceae and f_Ruminococcaceae (p < 0.05). Finally, a functional analysis indicated that altered microbes significantly changed the "Metabolism" pathway (p < 0.05). These findings suggested that saZnO could act as a feasible substitute for ZnO to reduce Zn emission and enhance growth performance, antioxidant and immune functions, and to adjust the structure of gut microbiota in piglets.

Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia.

Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30−300 mg/day and albumin/creatinine ratio 3−30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2’-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures.

Prediction injury of the central nervous system in the neonatal period in preterm newborns

Objective: to develop a system for predicting the probability of developing damage of the central nervoussystem (CNS) in the neonatal period in children who was born prematurely. Materials and methods: the main group of the study is premature newborns with gestational age (GA) less than 36 weeks inclusive (n = 60), the control group – fullterm newborns (n = 35). In the process of dynamic observation, the main group was divided into subgroups depending on the diagnosed CNS injury in the neonatal period, according to the neurosonography (intraventricular hemorrhages (IVH), periventricular leukomalacia (PVL): subgroup 1 (prematurity babies with CNS injury) – 25 people, subgroup 2 (premature babies without CNS injury) – 35 people. we estimated clinical and anamnestic, laboratory and instrumental data of children at birth and in dynamics, indicators of antioxidant protection (manganese-containing superoxide dismutase (Mn-SOD), copper, zinc-containing superoxide dismutase (Cu, Zn-SOD), reduced glutathione (GSH), oxidized glutathione (GSSG), total antioxidant capacity of blood (TAS/TAC), oxidative stress (TOS/TOC), 4 polymorphisms of Mn-SOD gene. Results: we designed two prognostic models which can determine the probability of developing IVH and PVL in the neonatal period in premature newborns. This models are included GA, Apgar scores at 1 and 5 minutes of life, presence of respiratory failure at birth, invasive mechanical ventilation in the neonatal period, presence of intrauterine infection in the neonatal period and indicators of antioxidant protection (GSH, TAS/TAC; model 2). Conclusions: a comprehensive assessment of the clinical and anamnestic data of premature newborns at birth, as well as the determination of indicators that take into account the level of antioxidant protection, will make it possible to identify a premature baby at the risk for organic injury of the CNS and to correct the therapeutic strategies in the neonatal period.

“Obesity and Insulin Resistance” Is the Component of the Metabolic Syndrome Most Strongly Associated with Oxidative Stress

Metabolic syndrome (MS) is not a homogeneous entity, but this term refers to the coexistence of factors that increase the risk for the development of type 2 diabetes and cardiovascular disease. There are different versions of the criteria for the diagnosis of MS, which makes the population of patients diagnosed with MS heterogeneous. Research to date shows that MS is associated with oxidative stress (OS), but it is unclear which MS component is most strongly associated with OS. The purpose of the study was to investigate the relationship between the parameters of OS and the presence of individual elements of MS in young adults, as well as to identify the components of MS by means of principal components analysis (PCA) and to investigate how the parameters of OS correlate with the presence of individual components. The study included 724 young adults with or without a family history of coronary heart disease (population of the MAGNETIC study). Blood samples were taken from the participants of the study to determine peripheral blood counts, biochemical parameters, and selected parameters of OS. In addition, blood pressure and anthropometric parameters were measured. In subjects with MS, significantly lower activity of superoxide dismutase (SOD), copper- and zinc-containing SOD (CuZnSOD), and manganese-containing SOD (MnSOD) were found, along with significantly higher total antioxidant capacity (TAC) and significantly lower concentration of thiol groups per gram of protein (PSH). We identified three components of MS by means of PCA: “Obesity and insulin resistance”, “Dyslipidemia”, and “Blood pressure”, and showed the component “Obesity and insulin resistance” to have the strongest relationship with OS. In conclusion, we documented significant differences in some parameters of OS between young adults with and without MS. We showed that “Obesity and insulin resistance” is the most important component of MS in terms of relationship with OS.

Determination of dietary copper requirement by the monoamine oxidase activity in kidney of broilers from 1 to 21 days of age.

The current dietary copper (Cu) requirement (8 mg/kg) of broilers is mainly based on growth, hemoglobin concentration, or hematocrit, which might not be the most sensitive indices to evaluate dietary Cu requirements of broilers. The present study was carried out to estimate dietary Cu requirements of broilers fed a conventional corn-soybean meal diet from 1 to 21 d of age using biochemical or molecular biomarkers. A total of 384 1-d-old Arbor Acres male broilers were randomly allocated to 1 of 6 treatments with 8 replicates and fed a Cu-unsupplemented corn-soybean meal basal diet containing 5.17 mg Cu/kg by analysis and the basal diet supplemented with 3, 6, 9, 12 or 15 mg Cu/kg as CuSO4⋅5H2O for 21 d. Regression analysis was performed to estimate the optimal dietary Cu level using the broken-line model. Dietary supplemental Cu level affected (P < 0.05) Cu contents in serum and liver and kidney monoamine oxidase (MAO) activity, but had no effects (P > 0.05) on the growth performance, Cu contents in heart, kidney, pancreas and spleen, Cu- and zinc-containing superoxide dismutase (CuZnSOD) activity and ceruloplasmin content in serum, CuZnSOD and cytochrome c oxidase (COX) activities and ceruloplasmin, CuZnSOD, MAO A, MAO B, COX4I1 and COX1 mRNA and protein expressions in the above tissues of broilers. As dietary supplemental Cu levels increased, Cu contents in serum and liver increased linearly (P < 0.05), but kidney MAO activity decreased linearly and quadratically (P < 0.05). The estimated dietary Cu requirement based on the fitted broken-line model (P = 0.035) of kidney MAO activity was 11.30 mg/kg. In conclusion, kidney MAO activity is a new and sensitive criterion to evaluate the dietary Cu requirement of broilers, and the dietary Cu requirement was 11.30 mg/kg for broilers fed the conventional corn-soybean meal diet from 1 to 21 d of age, which is higher than the current National Research Council (NRC) Cu requirement (8 mg/kg) of broilers.

Maternal Probiotic or Synbiotic Supplementation Modulates Jejunal and Colonic Antioxidant Capacity, Mitochondrial Function, and Microbial Abundance in Bama Mini-piglets.

The present study was conducted to investigate the effects of maternal probiotic or synbiotic supplementation during gestation and lactation on antioxidant capacity, mitochondrial function, and intestinal microbiota abundance in offspring weaned piglets. A total of 64 pregnant Bama mini-sows were randomly allocated into the control group (basal diet), antibiotic group (basal diet + 50 g/t virginiamycin), probiotic group (basal diet + 200 mL/d probiotics per pig), or synbiotic group (basal diet + 200 mL/d probiotics per pig + 500 g/t xylo-oligosaccharides). On day 30 of post-weaning, eight piglets per group with average body weight were selected for sample collection. The results showed that maternal probiotic supplementation increased the catalase (CAT) activity in plasma and glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities in plasma, jejunum, and colon of piglets while decreased the malondialdehyde (MDA) and H2O2 concentrations in plasma compared with the control group (P < 0.05). Moreover, maternal synbiotic supplementation increased the plasma CAT activity, jejunal glutathione and GSH-Px activities, jejunal and colonic total antioxidant capacity activity, and plasma and colonic SOD activity while decreased the colonic MDA concentration of offspring piglets compared with the control group (P < 0.05). The mRNA levels of antioxidant enzyme-related genes (copper- and zinc-containing superoxide dismutase, nuclear factor erythroid 2-related factor 1, and nuclear factor erythroid 2-related factor 2) and mitochondrial-related genes (adenosine triphosphate synthase alpha subunit, adenosine triphosphate synthase β, and mitochondrial transcription factor A) in the jejunal mucosa were significantly upregulated, while the level of colonic peroxisome proliferator-activated receptor γ coactivator-1α was downregulated by maternal synbiotic supplementation (P < 0.05). Maternal probiotic supplementation increased (P < 0.05) the Bacteroidetes abundance in the jejunum and Bifidobacterium abundance in the jejunum and colon, and synbiotic supplementation increased (P < 0.05) the abundances of Firmicutes, Bacteroidetes, Bifidobacterium, and Lactobacillus in the jejunum of piglets. Furthermore, correlation analysis revealed that intestinal microbiota abundances were significantly correlated with antioxidant enzyme activities and mitochondrial-related indexes. These findings indicated that maternal probiotic or synbiotic supplementation might be a promising strategy to improve the antioxidant capacity and mitochondrial function of offspring weaned piglets by altering the intestinal microbiota.

Neuroprotective Effects of Deuterium-Depleted Water (DDW) Against H2O2-Induced Oxidative Stress in Differentiated PC12 Cells Through the PI3K/Akt Signaling Pathway.

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Induction of endogenous antioxidants to act against oxidative stress-mediated neuronal damage seems to be a reasonable strategy for delaying the progression of such diseases. In this study, we investigated the neuroprotective effect of deuterium-depleted water (DDW) against H2O2-induced oxidative stress in differentiated PC12 cells and the possible signaling pathways involved. The differentiated PC12 cell line was pretreated with DDW containing different concentrations (50-100ppm) of deuterium and then treated with H2O2 to induce oxidative stress and neurotoxicity. We assessed cell survival, reactive oxygen species (ROS) generation, TUNEL assay, catalase (CAT), copper and zinc-containing superoxide dismutase (CuZn-SOD) and superoxide dismutase (SOD) activity and performed Western blot analysis to investigate the neuroprotective effect of DDW. The results indicated that DDW could attenuate H2O2-induced apoptosis, reduce ROS formation, and increase CAT, CuZn-SOD and SOD activity in H2O2-treated PC12 cells. Western blot analysis revealed that DDW treatment significantly increased the expression of p-Akt, Bcl-2 and GSK-3β. However, the protective effect of DDW on cell survival and the DDW-mediated increases in p-Akt, Bcl-2 and GSK-3β were abolished by pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002. In summary, DDW may protect differentiated PC12 cells against H2O2-induced oxidative stress through the PI3K/Akt signaling pathway.

Precompetitional Weight Reduction Modifies Prooxidative-Antioxidative Status in Judokas.

Objective The main aim of the study was an assessment of the influence of rapid weight loss on oxidative stress parameters in judokas differing in weight reduction value. Materials and Methods The study included 30 judokas with an age range of 18-30 years (mean age: 22.4 ± 3.40 years). Enzymatic and nonenzymatic antioxidative markers, lipid peroxidation markers, and total oxidative stress were assessed three times: one week before a competition (the first stage), after gaining the desired weight (the second stage), and one week after the competition (the third stage). Results Between the first and the second stage, the concentration of lipid hydroperoxides (LPH) decreased significantly. The superoxide dismutase (SOD), copper- and zinc-containing superoxide dismutase (Cu,Zn-SOD), ceruloplasmin (CER), malondialdehyde (MDA), LPH, and total oxidative stress (TOS) concentrations were the lowest one week after the competition. Linear regression indicated that the emphases on increased weight reduction increased the activity of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and protein sulfhydryl (PSH) between the first and the second stage of the study. Moderate weight reduction (2-5%) resulted in elevated levels of SOD, Mn-SOD, LPH, MDA, and TOS in comparison to low and high reductions. An opposite relation was observed in PSH. In judokas, the precompetitional weight reduction range was 0.44-6.10% (mean: 2.93% ± 1.76%) of the initial body weight. Concentrations of superoxide dismutase (SOD; p < .01), manganese-dependent superoxide dismutase (Mn-SOD; p < .001), and ceruloplasmin (CER; p < .05) decreased between the first and the third stage of the study as well between the second and third one. Before competitions, a decrease in lipid hydroperoxide (LPH; p < .01) concentration was observed. A reduction of malondialdehyde (MDA; p < .05), LPH (p < .01), and total oxidative stress (TOS; p < .05) levels between the first and the final stage occurred. The increase in weight reduction was linearly correlated with the rise of glutathione peroxidase (GPx; p < .05), glutathione reductase (GR; p < .05), glutathione S-transferase (GST; p < .05), and protein sulfhydryl (PSH; p < .05) concentrations between the first and the second stage of the study. Moderate weight reduction (2-5%) resulted in elevated levels of SOD (p < .05), Mn-SOD (p < .05), LPH (p < .05), MDA (p < .05), and TOS (p < .05) in comparison to low and high reductions. An opposite relation was observed in PSH (p < .005). Conclusions The effect of weight reduction in judo athletes on prooxidative-antioxidative system diversity depends on the weight reduction value.

Protective effects of whey on rat liver damage induced by chronic alcohol intake.

In 2012, alcohol liver disease resulted in 3.3 million-5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey ( per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper-zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling.

Decreased zinc and increased lead blood levels are associated with endometriosis in Asian Women

Endometriosis is an inflammatory disease associated with multiple pathogenic factors and studies regarding roles of trace metals in endometriosis have been inconsistent and limited. The aim of this cross-sectional study was to compare the blood levels of miscellaneous trace metals measured by inductively coupled plasma mass spectrometry in infertile women with and without endometriosis. Zinc level is associated with declining odds (adjusted OR=0.39, 95% CI=0.18–0.88) of endometriosis. By contrast, lead level is associated with increasing odds (adjusted OR=2.59, 95% CI=1.11–6.06) of endometriosis. The cadmium levels were higher in women with endometriosis, but the aOR was not significant. Zinc has anti-inflammatory characteristics and regulates homeostasis of zinc-containing superoxide dismutase. High lead levels might induce reactive oxygen species and deplete antioxidant defense mechanisms. Further prospective study is needed to test for their causal associations.

QM/MM Calculation of the Enzyme Catalytic Cycle Mechanism for Copper- and Zinc-Containing Superoxide Dismutase.

The entire enzyme catalytic mechanism including the electron and the proton transfers of the copper- and zinc-containing extracellular superoxide dismutase (SOD3) was investigated by using QM/MM method. In the first step, the electron transfer from O2·- to SOD3 occurred without the bond formation between the donor and the acceptor and formed the triplet oxygen molecule and reduced SOD3. In the reduced SOD3, the distorted tetrahedral structure of Cu(I) atom was maintained. The reduction of Cu(II) atom induced the protonation of His113, which bridges between the Cu(II) and Zn(II) atoms in the resting state. Since the protonation of His113 broke the bond between Cu(I) and His113, three-coordinated Cu(I) was formed. Further, we suggest the binding of O2·- formed hydrogen peroxide and the resting state after both the Cu reduction and the protonation of His113. The protonation of His113 caused the conformational change of Arg186 located at the entrance of the reactive site. The electrostatic potential surface around the reactive site showed that Arg186 plays an important role as electrostatic guidance for the negatively charged substrates only after the protonation of His113. The rotation of Arg186 switched the proton supply routes via Glu108 or Glu179 for transferring two protons from the bulk solvent.

Antioxidant Expression Response to Free Radicals in Active Men and Women Fallowing to a Session Incremental Exercise; Numerical Relationship Between Antioxidants and Free Radicals

BackgroundEnergy production is a necessary process to continue physical activities, and exercise is associated with more oxygen consumption and increase of oxidative stress. what seems important is the numerical relationship between antioxidant and free radicals. Although the activity of some enzymes increases with physical activities, but it is possible that gene expression of this enzyme is not changed during exercise.ObjectivesThe aim of the present study is to investigate the antioxidant enzymes gene expression and changes in malondialdehyde (MDA) and total antioxidant capacity (TAC) levels in men and women affected by a session of incremental exercise and to carefully and numerically assess the relationship between MDA changes and gene expression and activity of antioxidant enzymes.Materials and Methods12 active men and 12 active women (21 - 24 years old) participated voluntarily in this study. Peripheral blood samples were taken from the subjects in three phases, before and after graduated exercise test (GXT) and 3 hours later (recovery).ResultsThe gene expression of manganese superoxide dismutase (MnSOD) enzyme increased significantly in women in the recovery phase (P < 0.05). Catalase gene expression significantly increased in men in both phases (immediately & recovery) (P < 0.05). But the changes in active women were only significant immediately after the exercise. TAC levels increased significantly in men in the recovery phase and in active women immediately after the exercise (P < 0.05). MDA activity also increased significantly in men in both phases (P < 0.05). However, in women the increase was significant only in the recovery phase (P < 0.05). There was a reverse relationship between changes in MnSOD and copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) levels and MDA in men (P < 0.05). In active women there was also a significant relationship between changes in MDA and gene expression of Cu/ZnSOD and TAC (P < 0.05).ConclusionsThe increase in free radicals during incremental exercises challenges gene expression and activity of antioxidant enzymes. However, despite the negative effects of free radicals, in women, activity and gene expression of antioxidant enzymes respond appropriately to free radicals.

Effects of Edaravone on Hippocampal Antioxidants in EL Mice.

The role of oxidative stress in susceptibility to seizures has been the focus of several recent studies. The aim of the present study was to evaluate the antiepileptic effects of the free radical scavenger edaravone on EL mice, a strain that is highly susceptible to convulsive seizures. EL mice were treated intraperitoneally with edaravone or saline for 1 week. The levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and 3 isozymes of superoxide dismutase (SOD) (cytoplasmic copper- and zinc-containing SOD, extracellular SOD, and mitochondrial manganese-containing SOD) were measured in the hippocampus, and electroencephalograms (EEGs) were used to evaluate seizure sensitivity. Hippocampal levels of GSSG were lower in the edaravone group than in the untreated control group, and the GSH/GSSG ratio, Cu/Zn-SOD, and EC-SOD activities were higher in the edaravone group. Edaravone shortened the duration of interictal spike discharges and clinically suppressed epileptic seizures. Edaravone increases antioxidant potency and reduces seizure susceptibility in EL mice, making it a promising novel antiepileptic agent.

Antioxidant capacity and concentration of redox-active trace mineral in fully weaned intra-uterine growth retardation piglets.

BackgroundThe redox status of intra-uterine growth retardation (IUGR) piglets post-weaning has been poorly studied.MethodsNewborns from twenty-four sows were weighted, weaned at 21 d and fed a starter diet until sampling. Sampling was done at 14 d post-weaning. A piglet was defined as IUGR when its birth weight was 2 SD below the mean birth weight of the total population. At weaning, eighteen piglets with nearly equal body weight from each category (i.e. IUGR or normal birth weight (NBW) piglets) were selected and then allocated to two treatments, consisted of six replicates with each pen having three piglets.ResultsCompared with NBW group, IUGR significantly decreased average daily gain (P < 0.001), average daily feed intake (P = 0.003), and feed efficiency (P < 0.001) of piglets during the first two weeks post-weaning. IUGR decreased the activities of total antioxidant capacity (P = 0.019), total superoxide dismutase (T-SOD, P = 0.023), and ceruloplasmin (P = 0.044) but increased the levels of malondialdehyde (P = 0.040) and protein carbonyl (P = 0.010) in plasma. Similarly, the decreased activities of T-SOD (P = 0.005), copper- and zinc-containing superoxide dismutase (Cu/Zn-SOD, P = 0.002), and catalase (P = 0.049) was observed in the liver of IUGR piglets than these of NBW piglets. IUGR decreased hepatic Cu/Zn-SOD activity (P = 0.023) per unit of Cu/Zn-SOD protein in piglets when compared with NBW piglets. In addition, IUGR piglets exhibited the decreases in accumulation of copper in both plasma (P = 0.001) and liver (P = 0.014), as well as the concentrations of iron (P = 0.002) and zinc (P = 0.048) in liver. Compared with NBW, IUGR down-regulated mRNA expression of Cu/Zn-SOD (P = 0.021) in the liver of piglets.ConclusionsThe results indicated that IUGR impaired antioxidant capacity and resulted in oxidative damage in fully weaned piglets, which might be associated with the decreased levels of redox-active trace minerals. This study highlights the importance of redox status in IUGR offspring and provides a rationale for alleviating oxidative damage by dietary interventions aiming to supplement trace minerals and to restore redox balance in the future.

Mitochondrial Disease-related Mutation G167P in Cytochrome b of Rhodobacter capsulatus Cytochrome bc1 (S151P in Human) Affects the Equilibrium Distribution of [2Fe-2S] Cluster and Generation of Superoxide

Cytochrome bc1 is one of the key enzymes of many bioenergetic systems. Its operation involves a large scale movement of a head domain of iron-sulfur protein (ISP-HD), which functionally connects the catalytic quinol oxidation Qo site in cytochrome b with cytochrome c1. The Qo site under certain conditions can generate reactive oxygen species in the reaction scheme depending on the actual position of ISP-HD in respect to the Qo site. Here, using a bacterial system, we show that mutation G167P in cytochrome b shifts the equilibrium distribution of ISP-HD toward positions remote from the Qo site. This renders cytochrome bc1 non-functional in vivo. This effect is remediated by addition of alanine insertions (1Ala and 2Ala) in the neck region of the ISP subunit. These insertions, which on their own shift the equilibrium distribution of ISP-HD in the opposite direction (i.e. toward the Qo site), also act in this manner in the presence of G167P. Changes in the equilibrium distribution of ISP-HD in G167P lead to an increased propensity of cytochrome bc1 to generate superoxide, which becomes evident when the concentration of quinone increases. This result corroborates the recently proposed model in which "semireverse" electron transfer back to the Qo site, occurring when ISP-HD is remote from the site, favors reactive oxygen species production. G167P suggests possible molecular effects of S151P (corresponding in sequence to G167P) identified as a mitochondrial disease-related mutation in human cytochrome b. These effects may be valid for other human mutations that change the equilibrium distribution of ISP-HD in a manner similar to G167P.

Quercetin ameliorates liver injury induced with Tripterygium glycosides by reducing oxidative stress and inflammation.

Quercetin (Que) is one of main compounds in Lysimachia christinae Hance (Christina loosestrife), and has both medicinal and nutritional value. Glycosides from Tripterygium wilfordii Hook.f. (léi gōng téng [the thunder duke vine]; TG) have diverse and broad bioactivities but with a high incidence of liver injury. Our previous study reported on the hepatoprotective properties of an ethanol extract from L. christinae against TG-induced liver injury in mice. This research is designed to observe, for the first time, the possible protective properties of the compound Que against TG-induced liver injury, and the underlying mechanisms that are involved in oxidative stress and anti-inflammation. The results indicated that TG caused excessive elevation in serum levels of alanine/aspartate transaminase (ALT/AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), and pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α), as well as hepatic lipid peroxidation (all P < 0.01). On the other hand, following TG exposure, we observed significantly reduced levels of biomarkers, including hepatic glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), and the anti-inflammatory cytokine interleukin (IL)-10, as well as the enzyme activity and mRNA expression of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) (all P < 0.01). Nevertheless, all of these alterations were reversed by the pre-administration of Que or the drug bifendate (positive control) for 7 consecutive days. Therefore, this study suggests that Que ameliorates TG-induced acute liver injury, probably through its ability to reduce oxidative stress and its anti-inflammatory properties.

Geniposide protects against acute alcohol-induced liver injury in mice via up-regulating the expression of the main antioxidant enzymes.

Geniposide (GP) is one of main compounds in Gardenia jasminoides Ellis, with both medicinal and nutritional value. This study was designed to determine, for the first time, how GP from G. jasminoides protects against acute alcohol-induced liver injury, and the underlying mechanisms. Mice were orally administered alcohol (6.0 g/kg body mass) 2 h after intragastric administration of GP and bifendate, every day for 7 continuous days. Six hours after the alcohol was administered, levels of serum alanine/aspartate transaminase (ALT/AST), hepatic lipid peroxidation (LPO), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), copper- and zinc-containing superoxide dismutase (CuZn-SOD), and catalase (CAT), and mRNA expression of CuZn-SOD and CAT were assayed. The results demonstrated that GP (20.0, 40.0, or 80 mg/kg) significantly reversed the excessive, alcohol-induced elevation in both serum ALT/AST and hepatic LPO levels. Moreover, hepatic GSH, GST, GPx, CuZn-SOD, and CAT levels were all decreased in the alcohol-treated mice, whereas treatment with GP reversed these decreases. Further analysis indicated that hepatic mRNA expression of CuZn-SOD and CAT in the alcohol-treated mice was significantly down-regulated, whereas GP up-regulated such decreases. Taken together, this study shows that GP protects against acute alcohol-induced liver injury via up-regulating the expression of the main antioxidant enzymes, and thus ameliorates alcohol-induced oxidative stress injury in the liver.

The effects of wild-type and mutant SOD1 on smooth muscle contraction

In this work we compared the mutated liver copper zinc-containing superoxide dismutase (SOD1) protein G93A of the transgenic rat model of familial amyotrophic lateral sclerosis (FALS), to wild-type (WT) rat SOD1. We examined their enzymatic activities and effects on isometric contractions of uteri of healthy virgin rats. G93A SOD1 showed a slightly higher activity than WT SOD1 and, in contrast to WT SOD1, G93A SOD1 did not induce smooth muscle relaxation. This result indicates that effects on smooth muscles are not related to SOD1 enzyme activity and suggest that heterodimers of G93A SOD1 form an ion-conducting pore that diminishes the relaxatory effects of SOD1. We propose that this type of pathogenic feedback affects neurons in FALS.

Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo

The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B-induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity.

Superoxide Dismutases and Superoxide Reductases

Superoxide, O2•–, is formed in all living organisms that come in contact with air, and, depending upon its biological context, it may act as a signaling agent, a toxic species, or a harmless intermediate that decomposes spontaneously. Its levels are limited in vivo by two different types of enzymes, superoxide reductase (SOR) and superoxide dismutase (SOD). Although superoxide has long been an important factor in evolution, it was not so when life first emerged on Earth at least 3.5 billion years ago. At that time, the early biosphere was highly reducing and lacking in any significant concentrations of dioxygen (O2), very different from what it is today. Consequently, there was little or no O2•– and therefore no reason for SOR or SOD enzymes to evolve. Instead, the history of biological O2•– probably commences somewhere around 2.4 billion years ago, when the biosphere started to experience what has been termed the “Great Oxidation Event”, a transformation driven by the increase in O2 levels, formed by cyanobacteria as a product of oxygenic photosynthesis.1 The rise of O2 on Earth caused a reshaping of existing metabolic pathways, and it triggered the development of new ones.2 Its appearance led to the formation of the so-called “reactive oxygen species” (ROS), for example, superoxide, hydrogen peroxide, and hydroxyl radical, and to a need for antioxidant enzymes and other antioxidant systems to protect against the growing levels of oxidative damage to living systems. Dioxygen is a powerful four-electron oxidizing agent, and the product of this reduction is water. 1 When O2 is reduced in four sequential one-electron steps, the intermediates formed are the three major ROS, that is, O2•–, H2O2, and HO•. 2 3 4 5 Each of these intermediates is a potent oxidizing agent. The consequences of their presence to early life must have been an enormous evolutionary challenge. In the case of superoxide, we find the SOD and SOR enzymes to be widely distributed throughout current living organisms, both aerobic and anaerobic, suggesting that, from the start of the rise of O2 on Earth, the chemistry of superoxide has been an important factor during evolution. The SORs and three very different types of SOD enzymes are redox-active metalloenzymes that have evolved entirely independently from one another for the purpose of lowering superoxide concentrations. SORs catalyze the one-electron reduction of O2•– to give H2O2, a reaction requiring two protons per superoxide reacted as well as an external reductant to provide the electron (eq 6). SODs catalyze the disproportionation of superoxide to give O2 and H2O2, a reaction requiring one proton per superoxide reacted, but no external reductant (eq 7). 6 7 All of the SOR enzymes contain only iron, while the three types of SODs are the nickel-containing SODs (NiSOD), the iron- or manganese-containing SODs (FeSOD and MnSOD), and the copper- and zinc-containing SODs (CuZnSOD). Although the structures and other properties of these four types of metalloenzymes are quite different, they all share several characteristics, including the ability to react rapidly and selectively with the small anionic substrate O2•–. Consequently, there are some striking similarities between these otherwise dissimilar enzymes, many of which can be explained by considering the nature of the chemical reactivity of O2•– (see below). Numerous valuable reviews describing the SOD and SOR enzymes have appeared over the years, but few have covered and compared all four classes of these enzymes, as we attempt to do here. Thus, the purpose of this Review is to describe, compare, and contrast the properties of the SOR and the four SOD enzymes; to summarize what is known about their evolutionary pathways; and to analyze the properties of these enzymes in light of what is known of the inherent chemical reactivity of superoxide.