BACKGROUND

Recent studies have suggested augmentation in the inflammatory response as well as involvement of nitric oxide (NO) in mood disorders. Polymorphonuclear leukocytes (PMN), NO and free radicals have been associated with inflammatory response; however, the status of NO in the PMN has not been investigated so far in schizophrenia patients.

OBJECTIVE

The present study was undertaken to investigate levels of nitrite (a metabolite of NO), malonaldehyde (MDA, lipid peroxidation product) and antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (Gpx) in the PMN of schizophrenia patients.

METHODS

Patients with schizophrenia (n=62) were diagnosed according to DSM-IV and were free of anti-psychotic medications/ECT for at least 3 months. Mean age of the patients was 29.06+/-1.17 years, with a male to female ratio of 4:1, and mean duration of illness was 3.7+/-0.6 years. The control group consisted of 82 healthy subjects with a mean age of 37.0+/-1.26 and a male to female ratio of 5:1. PMN were isolated from the blood. Nitrite, MDA and antioxidant enzymes were estimated by standard biochemical techniques in the PMN of normal healthy controls and schizophrenia patients. Platelet and plasma nitrite levels were also estimated in controls and schizophrenia patients.

RESULTS

Nitrite content in the PMN was reduced to 68%, while plasma and platelet nitrite content in schizophrenia patients was not significantly changed in comparison to controls. Malonaldehyde (MDA) content in PMN was significantly augmented in schizophrenia patients but activity of SOD, catalase and Gpx remain unaltered.

CONCLUSIONS

Results obtained indicate a significant decrease in NO synthesis and an increase in MDA in the PMN of schizophrenia patients, while antioxidant enzyme activities were not altered in the PMN of schizophrenia patients. This suggests that the decrease in PMN NO synthesis by PMN might lead to oxidative stress in schizophrenia patients.

Hydroponic experiments were performed to investigate physiological mechanisms of selenium (Se) mitigation of Cd toxicity in rice. Exogenous Se markedly reduced Cd concentration in leaves, roots, and stems. Addition or pretreatment of <em>3</em> μM Se in 50 μM Cd solution significantly addressed Cd-induced growth inhibition, recovered root cell viability, and dramatically depressed O(2)(-), H(2)O(2), and malondialdehyde (MDA) accumulation. Supplemental Se counteracted 50 μM Cd-induced alterations of certain antioxidant enzymes, and uptake of nutrients, e.g. depressed Cd-induced increase in leaf and root superoxide dismutase (<em>SOD</em>) and leaf peroxidase (POD) activities, but elevated depressed catalase (CAT) activity; decreased Cd-induced high S and Cu concentrations in both leaves and roots. External Se counteracted the pattern of alterations in ATPase activities induced by Cd, e.g. significantly elevated the depressed root H(+)- and Ca(2+)-ATPase activities, but decreased the ascent root Na(+)K(+)-ATP activity. Results indicate that alleviated Cd toxicity by Se application is related to reduced Cd uptake and ROS accumulation, balanced nutrients, and increased H(+)- and Ca(2+)-ATPase activities in rice.

Cu,Zn-superoxide dismutase (<em>SOD</em>), Se-dependent glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione (GSH) play an important role in attenuating free radical-induced oxidative damage. The purpose of this research was to determine (1) whether sulfur dioxide (SO(2)) increases levels of lipid peroxidation and alters intracellular redox status in multiple organs of mice, and (2) whether SO(2) is a systemic toxic agent. The effect of SO(2) on levels of thiobarbituric acid-reactive substances (TBARS) and GSH and activities of <em>SOD</em>, GSH-Px, and CAT were investigated in nine organs (brain, lung, heart, liver, stomach, intestine, spleen, kidney, and testis) of Kunming albino mice of both sexes. SO(2) at 20 ppm (56 mg/m(<em>3</em>)) was administrated to the animals of SO(2) groups in an exposure chamber for 6 h/day for 7 days while control groups were exposed to filtered air in the same condition. Results show that SO(2) inhalation decreased significantly activities of <em>SOD</em> and GSH-Px in all organs tested in all SO(2) groups, with respect to their corresponding control groups; CAT activities in all organs tested of both sexual mice were significantly unaltered, except CAT activities in livers were significantly lowered by SO(2); SO(2) exposure decreased significantly GSH contents and significantly increased TBARS levels of all organs tested, in comparison with their respective control groups. These results lead to two conclusions: (1) SO(2) is a systemic oxidative damage agent. It results in a significant increase in the lipid peroxidation process in all organs tested of mice of both sexes, which is accompanied by changes of antioxidant status in these organs. (2) SO(2) may cause toxicological damage to multiple organs of animals, and it is suggested that the oxidative damage produced by SO(2) inhalation may influence or promote the progression or occurrence of some disease states of various organs, not only to respiratory system. Further work is required to understand the toxicological role of SO(2) on multiple or even all organs in mammals.

The purpose of this study was to characterize changes in antioxidant and age-related gene expression in aorta and aortic valve with aging, and test the hypothesis that increased mitochondrial oxidative stress accelerates age-related endothelial and aortic valve dysfunction. Wild-type (Mn<em>SOD</em>(+/+)) and manganese <em>SOD</em> heterozygous haploinsufficient (Mn<em>SOD</em>(+/-)) mice were studied at <em>3</em> and 18 mo of age. In aorta from wild-type mice, antioxidant expression was preserved, although there were age-associated increases in Nox2 expression. Haploinsufficiency of Mn<em>SOD</em> did not alter antioxidant expression in aorta, but increased expression of Nox2. When compared with that of aorta, age-associated reductions in antioxidant expression were larger in aortic valves from wild-type and Mn<em>SOD</em> haploinsufficient mice, although Nox2 expression was unchanged. Similarly, sirtuin expression was relatively well-preserved in aorta from both genotypes, whereas expression of SIRT1, SIRT2, SIRT<em>3</em>, SIRT4, and SIRT6 were significantly reduced in the aortic valve. Expression of p16(ink4a), a marker of cellular senescence, was profoundly increased in both aorta and aortic valve from Mn<em>SOD</em>(+/+) and Mn<em>SOD</em>(+/-) mice. Functionally, we observed comparable age-associated reductions in endothelial function in aorta from both Mn<em>SOD</em>(+/+) and Mn<em>SOD</em>(+/-) mice. Interestingly, inhibition of NAD(P)H oxidase with apocynin or gp91ds-tat improved endothelial function in Mn<em>SOD</em>(+/+) mice but significantly impaired endothelial function in Mn<em>SOD</em>(+/-) mice at both ages. Aortic valve function was not impaired by aging or Mn<em>SOD</em> haploinsufficiency. Changes in antioxidant and sirtuin gene expression with aging differ dramatically between aorta and aortic valve. Furthermore, although Mn<em>SOD</em> does not result in overt cardiovascular dysfunction with aging, compensatory transcriptional responses to Mn<em>SOD</em> deficiency appear to be tissue specific.

(1) The role of activation of Rho-kinase in the pathogenesis of cognitive deficit and neuronal damage caused by chronic global ischemia is not clear. In this study, hydroxyfasudil, a Rho-kinase inhibitor, was found to improve the learning and memory performance significantly in rats with ischemia induced by chronic cerebral hypoperfusion after permanent bilateral carotid artery ligation (BCAL). This was observed by the administration of hydroxyfasudil (1 mg/kg or 10 mg/kg, once per day for <em>3</em>0 days) to ischemic rats and the measurements of escape latency and time spent in the target quadrant among the ischemic, sham, and ischemic plus hydroxyfasudil rats by the method of Morris water maze. (2) In electrophysiological study, hydroxyfasudil abolished the inhibition of long-term potentiation (LTP) in rats with ischemia. Morphologically, it also markedly reduced pathological changes such as neuronal cells loss and nuclei shrinkage in cortex and hippocampus of ischemic rats. Biochemical analysis showed that the inhibition of Rho-kinase by hydroxyfasudil reduced the amount of MDA and increased the activities of <em>SOD</em> and GPx in ischemic rats that had increased MDA and decreased <em>SOD</em> and GPx activities. (<em>3</em>) To explore mechanism (s) of the beneficial effects of hydroxyfasudil in ischemia, we performed immunohistochemistry and RT-PCR analyses of NMDA NR2B subunit and for the first time found that hydroxyfasudil increased the expression of NR2B in cortex and hippocampus at both protein and mRNA levels. (4) Taken together, our data further support the notion that the inhibition of Rho-kinase provides neuroprotective effects in cerebral ischemia.

This study examined the effect of increasing chloroplastic superoxide dismutase (<em>SOD</em>), ascorbate peroxidase (APX), or glutathione reductase (GR) activity via plant transformation of cotton on the initial recovery of photosynthesis following exposures to 10 degrees C and high photon flux density (PFD). Growing wild-type or non-expressing segregate plants (controls) and transformants at two PFDs (600 micromol m(-2) s(-1) and full sun) resulted in a range of total antioxidant enzyme activities. Total <em>SOD</em> activities above that for control leaves grown in full sun did not substantially improve the recoveries of CO(2)-saturated photosynthesis, especially for stress treatments lasting more than 1 h, while elevated APX or GR activity did improve recoveries after 1-<em>3</em> h of the chilling treatment. No synergistic effects were noted when the activities of more than one antioxidant enzyme were elevated in transgenic hybrids. Although these results suggest that the protection of photosynthesis can be realized by reducing either superoxide or H(2)O(2) levels, thereby reducing the possibility of hydroxyl radical formation, the situation is complicated, since elevated APX or GR activity can improve recoveries even when additional <em>SOD</em> activity has no effect. In conclusion, to enhance the protection of photosynthesis using stroma-targeted antioxidant enzymes, enhancing metabolism associated with H(2)O(2) is more effective than enhancing the capacity for superoxide scavenging. Although small, the improvement in the protection of photosynthetic capacity may be sufficient to improve cotton yield in temperate regions with large diurnal temperature fluctuations.

Metal and alloy nanomaterials have intriguing oxidase- and superoxide dismutation-like (<em>SOD</em>-like) activities. However, origins of these activities remain to be studied. Using density functional theory (DFT) calculations, we investigate mechanisms of oxidase- and <em>SOD</em>-like properties for metals Au, Ag, Pd and Pt and alloys Au4-xMx (x = 1, 2, <em>3</em>; M = Ag, Pd, Pt). We find that the simple reaction-dissociation of O2-supported on metal surfaces can profoundly account for the oxidase-like activities of the metals. The activation (Eact) and reaction energies (Er) calculated by DFT can be used to effectively predict the activity. As verification, the calculated activity orders for series of metal and alloy nanomaterials are in excellent agreement with those obtained by experiments. Briefly, the activity is critically dependent on two factors, metal compositions and exposed facets. On the basis of these results, an energy-based model is proposed to account for the activation of molecular oxygen. As for <em>SOD</em>-like activities, the mechanisms mainly consist of protonation of O2(•-) and adsorption and rearrangement of HO2(•) on metal surfaces. Our results provide atomistic-level insights into the oxidase- and <em>SOD</em>-like activities of metals and pave a way to the rational design of mimetic enzymes based on metal nanomaterials. Especially, the O2 dissociative adsorption mechanism will serve as a general way to the activation of molecular oxygen by nanosurfaces and help understand the catalytic role of nanomaterials as pro-oxidants and antioxidants.

It has been suggested that antioxidants play a role in regulating or modulating senescence dynamics of plant tissues. Ethylene has been shown to promote early plant senescence while controlled atmospheres (CA; reduced O2 levels and elevated CO2 levels) can delay its onset and/or severity. In order to examine the possible importance of various antioxidants in the regulation of senescence, detached spinach (Spinacia oleracea L.) leaves were stored for <em>3</em>5 d at 10 degrees C in one of three different atmospheres: (1) ambient air (0.<em>3</em>% CO2, 21.5% O2, 78.5% N2), (2) ambient air + 10 ppm ethylene to promote senescence, or (<em>3</em>) CA (10% CO2, 0.8% O2 and 89.2% N2) to delay senescence. At weekly intervals, material was assessed for activities of the antioxidant enzymes ascorbate peroxidase (ASPX; EC 1.11.1.11), catalase (CAT; EC 1.11.1.6), dehydroascorbate reductase (DHAR; EC 1.8.5.4), glutathione reductase (GR; EC 1.6.4.2), monodehydroascorbate reductase (MDHAR; EC 1.6.5.4), and superoxide dismutase (<em>SOD</em>; EC 1.15.1.1), and concentrations of the water-soluble antioxidant compounds ascorbate and glutathione. Indicators of the rate and severity of senescence (lipid peroxidation, chlorophyll, and soluble protein levels) were also determined. Results indicated that the rate and severity of senescence was similar between the leaves stored in ambient air or CA until day <em>3</em>5, at which point the ambient air-stored leaves exhibited a sharp increase in lipid peroxidation. Tissues under both storage regimes demonstrated significant declines only in levels of ASPX, CAT, and ascorbate. Glutathione content in the CA-stored tissue also significantly dropped, but only on day <em>3</em>5. In contrast, spinach leaves stored in ambient air + ethylene experienced a rapid decrease in levels of all the antioxidants assessed except <em>SOD</em>. Declines in levels of ASPX, CAT, and ascorbate over the <em>3</em>5 d storage period regardless of the composition of the storage atmosphere suggests that regulation of H2O2 levels plays an important role in both the dynamics and severity of post-harvest senescence of spinach.

Cadmium (Cd), one of the most toxic environmental and industrial pollutants, is known to exert gonadotoxic and spermiotoxic effects. In the present study, we examined the toxic effect of Cd on the testis of freshwater crab, Sinopotamon henanense. Crabs were exposed to different Cd concentrations (from 0 to 116.00 mg·L(-1)) for 7 d. Oxidative stress and apoptotic changes in the testes were detected. The activities of <em>SOD</em>, GPx and CAT initially increased and subsequently decreased with increasing Cd concentrations, which was accompanied with the increase in malondialdehyde (MDA) and H(2)O(2) content in a concentration-dependent manner. Typical morphological characteristic and physiological changes of apoptosis were observed using a variety of methods (HE staining, AO/EB double fluorescent staining, Transmission Electron Microscope observation and DNA fragmentation analysis), and the activities of caspase-<em>3</em> and caspase-9 were increased in a concentration-dependent manner after Cd exposure. These results led to the conclusion that Cd could induced oxidative damage as well as apoptosis in the testis, and the apoptotic processes may be mediated via mitochondria-dependent apoptosis pathway by regulating the activities of caspase-<em>3</em> and caspase-9.

The present study was designed to investigate the potential role of miR-2<em>3</em>a-<em>3</em>p in experimental brain ischemia-reperfusion injury. Cerebral ischemia reperfusion was induced by transient middle cerebral artery occlusion (MCAO) for 1h in C57/BL6 mice. And miR-2<em>3</em>a-<em>3</em>p angomir was transfected to upregulate the miR-2<em>3</em>a-<em>3</em>p level. Our results showed that miR-2<em>3</em>a-<em>3</em>p levels were transiently increased at 4h after reperfusion in the peri-infarction area, while markedly increased in the infarction core at reperfusion 4h and 24h. Importantly, in vivo study demonstrated that miR-2<em>3</em>a-<em>3</em>p angomir treatment through intracerebroventricular injection markedly decreased cerebral infarction volume after MCAO. Simultaneously, miR-2<em>3</em>a-<em>3</em>p reduced peroxidative production nitric oxide (NO) and <em>3</em>-nitrotyrosine (<em>3</em>-NT), and increased the expression of manganese superoxide dismutase (Mn<em>SOD</em>). In vitro study demonstrated that miR-2<em>3</em>a-<em>3</em>p decreased hydrogen peroxide (H2O2)-induced lactate dehydrogenase (LDH) leakage dose-dependently, and reduced protein levels of activated caspase-<em>3</em> in neuro-2a cells. In addition, miR-2<em>3</em>a-<em>3</em>p reduced H2O2-induced production of NO and <em>3</em>-NT dose-dependently, and reversed the decreased activity of total <em>SOD</em> and Mn<em>SOD</em> in neuro-2a cells. Our study indicated that miR-2<em>3</em>a-<em>3</em>p suppressed oxidative stress and lessened cerebral ischemia-reperfusion injury.

BACKGROUND

Higher aluminum (Al) content in infant formula and its effects on neonatal brain development are a cause for concern. This study aimed to evaluate the distribution and concentration of Al in neonatal rat brain following Al treatment, and oxidative stress in brain tissues induced by Al overload.

METHODS

Postnatal day <em>3</em> (PND <em>3</em>) rat pups (n =46) received intraperitoneal injection of aluminum chloride (AlCl<em>3</em>), at dosages of 0, 7, and <em>3</em>5 mg/kg body wt (control, low Al (LA), and high Al (HA), respectively), over 14 d.

RESULTS

Aluminum concentrations were significantly higher in the hippocampus (751.0 ± 225.8 ng/g v.s. 294.9 ± 180.8 ng/g; p < 0.05), diencephalon (79.6 ± 20.7 ng/g v.s. 20.4 ± 9.6 ng/g; p < 0.05), and cerebellum (144.8 ± <em>3</em>6.2 ng/g v.s. 8<em>3</em>.1 ± 15.2 ng/g; p < 0.05) in the HA group compared to the control. The hippocampus, diencephalon, cerebellum, and brain stem of HA animals displayed significantly higher levels of lipid peroxidative products (TBARS) than the same regions in the controls. However, the average superoxide dismutase (SOD) activities in the cerebral cortex, hippocampus, cerebellum, and brain stem were lower in the HA group compared to the control. The HA animals demonstrated increased catalase activity in the diencephalon, and increased glutathione peroxidase (GPx) activity in the cerebral cortex, hippocampus, cerebellum, and brain stem, compared to controls.

CONCLUSIONS

Aluminum overload increases oxidative stress (H2O2) in the hippocampus, diencephalon, cerebellum, and brain stem in neonatal rats.

It has been reported that exercise induces oxidative stress and causes adaptations in antioxidant defences. The aim of this study was to determine the adaptations of lymphocytes to the oxidative stress induced by an exhaustive exercise. Nine voluntary male subjects participated in the study. The exercise was a cycling mountain stage (171.8 km), and the cyclists took a mean of 28<em>3</em> min to complete it. Blood samples were taken the morning of the cycling stage day, after overnight fasting, and <em>3</em> h after finishing the stage. We determined the blood glutathione redox status (GSSG/GSH), lymphocyte antioxidant enzyme activities and superoxide dismutase (<em>SOD</em>) levels; the plasma and lymphocyte vitamin E levels; the serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities and urate levels; the plasma carotene and malonaldehyde (MDA) levels; and the lymphocyte carbonyl index. The cycling stage induced significant increases in blood-oxidized (glutathione/GSSG), plasma MDA and serum urate levels. The exercise also produced increases in CK and LDH serum activities. The mountain cycling stage induced significant increases in lymphocyte vitamin E levels, glutathione peroxidase and glutathione reductase activities as well as increased <em>SOD</em> activity and protein levels. The protein carbonyl levels increased significantly in lymphocytes after the stage. In conclusion, in spite of increasing antioxidant defences in response to the oxidative stress induced by the exhaustive exercise, lymphocyte oxidative damage was produced after the stage as demonstrated by the increased carbonyl index even in very well trained athletes.

BACKGROUND

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Hydrogen sulfide (H2S) plays an important role in physiology and pathophysiology of liver. However, whether exogenous H2S could mitigate the hepatic steatosis in mice remains unclear. The aim of this study is to evaluate the effects of H2S on fatty liver.

METHODS

C57BL/6 mice were fed with either a high-fat diet (HFD) or a normal fat diet (NFD) for 16 weeks. After 12 weeks of feeding, the HFD-fed mice were injected one time per day with NaHS or saline for the followed 4 weeks.

RESULTS

Compared to NFD, HFD could induce an accumulation of lipids in liver and a damage of hepatic structure. Compared to saline treatment, in the liver of HFD fed mice H2S treatment could significantly (1) recover the structure; (2) decrease the accumulation of lipids including triglyceride (TG) and total cholesterol (TC); (<em>3</em>) decrease the expression of fatty acid synthase (FAS) and increase the expression of carnitine palmitoyltransferase-1 (CPT-1); (4) reduce malondialdehyde (MDA) levels; (5) increase the activities of superoxide dismutase (<em>SOD</em>) and glutathione peroxidase (GPx).

CONCLUSIONS

H2S could mitigate the fatty liver by improving lipid metabolism and antioxidant potential in HFD-induced obese mice.

Cumulative evidence demonstrates that apoptosis caused by oxidative stress plays a key role in neuronal cell death after transient focal cerebral ischemia. In this study, we investigated exactly the immunohistochemical alterations of neuronal nuclei (NeuN), Cu/Zn-<em>SOD</em> (superoxide dismutase), Mn-<em>SOD</em>, 4-hydroxy-2-nonenal (HNE), and single strand DNA (ssDNA) in the striatum from <em>3</em> h up to 15 days after transient focal cerebral ischemia in rats under the same conditions. A conspicuous decrease of NeuN immunoreactive neurons was observed in the ipsilateral striatum from <em>3</em> h up to 15 days after focal ischemia. For Cu/Zn-<em>SOD</em>, Mn-<em>SOD</em> and HNE immunostainings, the alteration of Cu/Zn-<em>SOD</em> and HNE immunoreactivity was more pronounced than that of Mn-<em>SOD</em> immunoreactivity in the shrunken or atrophic neurons of ipsilateral striatum <em>3</em> h after focal ischemia. Thereafter, a significant increase of HNE immunoreactivity was observed in the shrunken or atrophic neurons of ipsilateral striatum up to 15 days after focal ischemia. In contrast, a significant decrease of Cu/Zn-<em>SOD</em> immunoreactivity was found in the ipsilateral striatum from <em>3</em> up to 15 days after focal ischemia. On the other hand, a significant increase of Mn-<em>SOD</em> immunereactivity was observed in the ipsilateral striatum from 1 up to 7 days after focal ischemia. In addition, our Western blot analysis also showed a significant increase of Cu/Zn-<em>SOD</em> and Mn-<em>SOD</em> in the ipsilateral striatum 1 day after focal ischemia, as compared to sham-operated group. In contrast, a significant increase in the number of ssDNA immunoreactive apoptotic neurons was observed in the ipsilateral striatum from <em>3</em> h to <em>3</em> days after focal cerebral ischemia. The present results also suggest that increased reactive oxygen species (ROS) production during reperfusion may contribute to the induction of the alteration of lipid peroxidation and could thereby lead to apoptosis in neurons of the ipsilateral striatum after transient focal ischemia, because of an insufficient expression of Cu/Zn-<em>SOD</em> and Mn-<em>SOD</em>. Furthermore, our findings demonstrate that the lipid peroxidation against mitochondrial membrane may contribute to apoptosis of striatal neurons after transient focal ischemia. Thus our findings demonstrate that the protection of lipid peroxidation against mitochondrial membrane may offer a novel therapeutic strategy for brain stroke in humans.

We examined the activity of striatal superoxide dismutase (<em>SOD</em>) in two acute pharmacological models of Huntington's disease (HD), and compared it with <em>SOD</em> activity in the striata of mice transgenic for the HD mutation. Total <em>SOD</em>, and Cu/Zn<em>SOD</em> activities increased in young transgenic mice, but decreased in older (<em>3</em>5 week) mice. We consider that the increased enzyme activity represents a compensatory mechanism to protect cells from free radical-induced damage, but the system becomes insufficient in older animals. Major decreases in <em>SOD</em> activity were also observed both after quinolinic acid and <em>3</em>-nitropropionic acid intrastriatal injections. The present results indicate that in both types of HD models striatal oxidative damage occurs, and that it is associated with alterations in the cellular antioxidant system.

Salt stress is a major abiotic stress that limits crop productivity in many regions of the world. A comparative proteomic approach to identify salt stress-responsive proteins and to understand the molecular mechanisms was carried out in the woody halophyte Kandelia candel. Four-leaf-old K. candel seedlings were exposed to 150 (control), <em>3</em>00, 450, and 600 mM NaCl for <em>3</em> days. Proteins extracted from the leaves of K. candel seedlings were separated by two-dimensional gel electrophoresis (2-DE). More than 900 protein spots were detected on each gel, and 5<em>3</em> differentially expressed protein spots were located with at least two-fold differences in abundance on 2-DE maps, of which 48 were identified by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF-TOF/MS). The results showed that K. candel could withstand up to 450 mM NaCl stress by up-regulating proteins that are mainly involved in photosynthesis, respiration and energy metabolism, Na(+) compartmentalization, protein folding and assembly, and signal transduction. Physiological data, including superoxide dismutase (<em>SOD</em>) and dehydroascorbate reductase (DHAR) activities, hydrogen peroxide (H2O2) and superoxide anion radicals (O2(-)) contents, as well as Na(+) content and K(+)/Na(+) ratios all correlated well with our proteomic results. This study provides new global insights into woody halophyte salt stress responses. Identification of differentially expressed proteins promotes better understanding of the molecular basis for salt stress reduction in K. candel.

Oxidative-free radicals and apoptosis have linked to chronic skin diseases. Higher levels of oxidative radicals and the release of mitochondrial cytochrome c may have a role in the pathogenesis of psoriasis. We investigated the possible role of cellular oxidative stress and release of cytochrome c of mitochondria in the pathogenesis of psoriasis. Disease severity was assessed by psoriasis area severity index score (PASI) of 55 psoriasis patients, they grouped as mild (11), moderate (20) and severe (24), also 20 healthy individuals used as controls. All groups were subjected for serum malondialdehyde (MDA), nitric oxide (NO·), superoxide dismutase (<em>SOD</em>), catalase (CAT), total antioxidant status (TAS) and serum cytochrome c concentrations. We found that, (1) Severity wise increase in MDA and NO·, and decrease in <em>SOD</em>, CAT and TAS levels in all patients with different degrees of psoriasis; (2) PASI showed positive correlation with the increase in MDA and NO·, and negatively with decreased <em>SOD</em>, CAT and TAS levels; (<em>3</em>) significant increase in cytochrome c level was observed among psoriasis patients which showed negative correlation to MDA and NO· levels in mild and positively with moderate and severe groups. The release of mitochondrial cytochrome c indicates the induction of apoptosis mediated via oxidative stress which ultimately plays role in the pathogenesis of psoriasis.

Apigenin, a plant-derived flavonoid, was investigated to determine whether it could influence hydrogen peroxide (H2O2)-induced oxidative damage and cellular dysfunction in the MC<em>3</em>T<em>3</em>-E1 mouse osteoblastic cell line. In the present study, osteoblastic cells were treated with H2O2 in the presence or absence of apigenin. Cell viability, apoptosis, reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm) were subsequently examined. It was observed that H2O2 reduced cell survival and ΔΨm, while it markedly increased the intracellular levels of ROS and apoptosis. However, pretreatment of cells with apigenin attenuated all the H2O2-induced effects. The antioxidants, catalase and N-acetyl-L-cysteine (NAC) also prevented H2O2-induced oxidative cell damage. In addition, treatment with apigenin resulted in a significant elevation of osteoblast differentiation genes including alkaline phosphatase (ALP), collagen, osteopontin (OPN), osteoprotegerin (OPG), bone sialoprotein (BSP), osterix (OSX) and osteocalcin (OC) and bone morphogenetic proteins (BMPs) genes (BMP2, BMP4 and BMP7). In the mechanistic studies of cell signaling by the antioxidative potential of apigenin, it was found that apigenin activated the H2O2-induced decreased expression of phosphatidylinositol <em>3</em>'-kinase (PI<em>3</em>K), protein kinase B2 (AKT2) genes and extracellular signal-related kinase (EPK) 2, which are key regulators of survival-related signaling pathways. By contrast, there were no changes in the expression of nuclear facor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) gene exposed to H2O2 in the present study. Apigenin also upregulated the gene expression of antioxidant enzymes, superoxide dismutase (<em>SOD</em>) 1, <em>SOD</em>2 and glutathione peroxidase (GPx) 1. Taken together, these results suggested that apigenin attenuated oxidative-induced cell damage in osteoblastic cells and may be useful for the treatment of oxidative-related bone disease.

BACKGROUND

This study aimed at comparing the effects of feeding mice and rats with adenine to induce a state of chronic renal failure (CRF), and to assess the effect of treatment with gum acacia (GA) thereon.

METHODS

We compared the outcome, in mice, of feeding adenine at three different doses (0.75%, 0.<em>3</em>%, and 0.2%, w/w). Biochemical and histopathological studies were conducted in plasma, urine and renal homogenates from both species.

RESULTS

When mice and rats were fed adenine (0.75%, w/w), all treated rats survived the treatment, but all treated mice died within 1-2 days. The dosage in mice was reduced to 0.<em>3</em>%, w/w, for 4 weeks, but again all treated mice died within <em>3</em>-4 days. A further reduction in the dosage in mice to 0.2%, w/w, for 4 weeks resulted in no mortality, and produced alterations similar to those observed in rats fed adenine at a dose of 0.75%,w/w, for 4 weeks. Plasma creatinine, urea and urinary protein were significantly increased (P<0.001) in adenine-treated mice and rats, and this action was incompletely, but significantly (P<0.05), reversed by GA. Adenine significantly (P<0.001) reduced superoxide dismutase (<em>SOD</em>) activity and reduced glutathione (GSH) concentration in renal homogenates from both species, and these reductions were significantly (P<0.05) ameliorated by GA.

CONCLUSIONS

Our data suggest that mice are more sensitive to adenine than rats, and that a dose of adenine of 0.2%, w/w, for 4 weeks in mice is suggested as a model for CRF. In both models, GA (15%, w/v, in the drinking water for 4 weeks) given concomitantly with adenine ameliorated the severity of CRF to a similar extent.

BACKGROUND

Ischemia followed by reperfusion leads to acute renal failure in both native kidneys and a renal allograft. Our previous study found that transplantation of mesenchymal stem cells (MSCs) ameliorated ischemia-reperfusion (I/R)-induced kidney dysfunction by increasing the activities of antioxidant enzymes. The purpose of this study was to evaluate whether intra-arterial versus intravenous administration was more effective.

METHODS

Renal ischemia was induced by clamping the right renal vessels for 60 minutes after removal of the left kidney. MSCs (1 × 10(6)) were administered through either the tail vein (TV) or the renal arter (RA), followed by reperfusion. We evaluated kidney function as well as tissue activities of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Histopathologic and immunohistochemical examinations were performed. To tracking MSCs in vivo, they were transfected with firefly luciferase and monomeric red fluorescent protein reporter genes (fluc-mrfp). MSC retention and survival were assessed using bioluminescence imaging. We observed the effects of MSCs (1 × 10(6), 2 × 10(6), and 5 × 10(6)) on IR injury.

RESULTS

MSC infusion via either the tail vein or the renal artery significantly improved kidney function at days 1, 3, and 5 as indicated by lower urea and creatinine levels compared with vehicle controls (P < .05). I/R induced a reduction in renal tissue SOD activity but GSH-PX was significantly improved by MSCs (P < .05) on day 1. Treatment with MSCs also significantly reduced renal tissue MDA levels that had been otherwise increased by renal I/R injury (P < .05). The above parameters were similar between the TV and the RA groups. Histological examination revealed kidneys from MSC-treated rats to show fairly normal morphology. The percentages of proliferating cell nuclear antigen (PCNA)-positive cells were higher in the MSC groups: 16.83 ± 4.62%, 19.17 ± 6.21%, and 2.17 ± 1.16% for the TV, RA, and control groups, respectively. There was no significant dose-related difference among MSC groups. Bioluminescence imaging demonstrated most MSCs to be lost within 7 days after either intravenous or intra-arterial infusion.

CONCLUSIONS

MSCs ameliorated I/R-induced acute renal failure in rats with similar efficiency whether infused either through the TV or the RA. There was no dose-dependent responses.

Melatonin influences intestinal microbiota and the pathogenesis of various diseases. This study was conducted to explore whether melatonin alleviates weanling stress through intestinal microbiota in a weanling mouse model. Melatonin supplementation in weanling mice (provided in the drinking water at a dosage of 0.2 mg/mL for 2 weeks) significantly improved body weight gain (1.4 ± 0.0<em>3</em> g/day in melatonin group vs 1.2 ± 0.06 g/day in control group) and intestinal morphology (ie, villus length, crypt depth, and villus to crypt ratio), but had little effect on the proliferation or apoptosis of intestinal cells, the numbers of Paneth cells and goblet cells, as well as the expression of makers related to enterocytes (sucrase) and endocrine cells (chromogranin A and peptide YY) in the ileum. Melatonin supplementation had little effect on serum levels of amino acids or stress-related parameters (eg, <em>SOD</em>, TNF-α, and angiotensin I). 16S rRNA sequencing suggested that melatonin supplementation increased the richness indices of intestinal microbiota (observed species, Chao 1, and ACE) and shaped the composition of intestinal microbiota (eg, increase in the abundance of Lactobacillus [19 ± <em>3</em>% in melatonin group vs 6 ± 2% in control group]), which was demonstrated using an ex vivo proliferation assay and colonic loop proliferation assay. Melatonin supplementation also significantly influenced the metabolism of intestinal microbiota, such as amino acid metabolism and drug metabolism. More importantly, in antibiotic-treated weanling mice and germ-free weanling mice, melatonin failed to affect body weight gain or intestinal morphology. Melatonin significantly reduced (by about 60%) the bacterial load in enterotoxigenic Escherichia coli (ETEC)-infected weanling mice, but had little effect on ETEC load in antibiotic-pretreated animals. In conclusion, melatonin affects body weight gain, intestinal morphology, and intestinal ETEC infection through intestinal microbiota in weanling mice. The findings highlight the importance of intestinal microbiota in mediating the various physiological functions of melatonin in the host.

The structural integrity of apolipoprotein A-I (apo A-I) is critical to the physiological function of high-density lipoprotein (HDL). Oxidized lipoproteins are thought to be of central importance in atherogenesis, and oxidation products characteristic of myeloperoxidase, a heme protein secreted by activated phagocytes, have been detected in human atherosclerotic tissue. At plasma concentrations of halide ion, hypochlorous acid is a major product of the myeloperoxidase-hydrogen peroxide-chloride system. We therefore investigated the effects of activated human neutrophils, a potent source of myeloperoxidase and hydrogen peroxide, on the protein and lipid components of HDL. Both free and HDL-associated apo A-I exposed to activated human neutrophils underwent extensive degradation as monitored by RP-HPLC and Western blotting with a polyclonal antibody to apo A-I. Replacement of the neutrophils with reagent HOCl resulted in comparable damage (at molar oxidant : HDL subclass <em>3</em> ratio = 100) as observed in the presence of activated phagocytes. Apo A-I degradation by activated neutrophils was partially inhibited by the HOCl scavenger methionine, by the heme inhibitor azide, by chloride-free conditions, by the peroxide scavenger catalase, and by a combination of superoxide dismutase (<em>SOD</em>)/catalase, implicating HOCl in the cell-mediated reaction. The addition of a protease inhibitor (<em>3</em>,4-dichloroisocoumarin) further reduced the extent of apo A-I damage. In contrast to the protein moiety, there was little evidence for oxidation of unsaturated fatty acids or cholesterol in HDL<em>3</em> exposed to activated neutrophils, suggesting that HOCl was selectively damaging apo A-I. Our observations indicate that HOCl generated by myeloperoxidase represents one pathway for protein degradation in HDL<em>3</em> exposed to activated phagocytes.

Alzheimer's disease (AD) is characterized by progressive cognitive deficits, accumulation of amyloid-β (Aβ) and intracellular neurofibrillary tangles, and neuronal death. Additionally, mitochondrial dysfunction and free radical damage are hallmarks of AD brain. Here we set out to define the role of oxidative stress in AD pathogenesis and progression by chronically treating <em>3</em>xTg-AD mice with the superoxide dismutase (<em>SOD</em>)/catalase mimetic, EUK-207. Treatment started at 4 months before onset of pathology and cognitive deficits, and continued until 9 months, when the AD phenotype was established. Cognitive performance was assessed using fear conditioning, and brain oxidative stress, Aβ, and tau pathology were analyzed. At 9 months, <em>3</em>xTg-AD mice exhibited a decline in performance in both contextual and cued fear conditioning, as compared to wild-type mice. EUK-207-treated <em>3</em>xTg-AD mice did not display any deficit in fear conditioning and exhibited reduced Aβ, tau, and phosphorylated tau accumulation in amygdala and hippocampus, as well as brain levels of Aβ42, oxidized nucleic acids, and lipid peroxidation. The effects of a <em>3</em>-month treatment after pathology onset at 9 months on cognitive performance, brain oxidative stress, Aβ, and tau pathology were also evaluated. EUK-207-treated <em>3</em>xTg-AD mice did not display any deficit in fear conditioning and were protected against increases in brain levels of oxidized nucleic acids and lipid peroxidation; they also had reduced Aβ, tau, and hyperphosphorylated tau accumulation in amygdala and hippocampus. Our results confirm a critical role for oxidative stress in AD pathogenesis and progression and suggest the potential usefulness of EUK-207 in AD treatment.

Changes in activities of antioxidant enzymes including superoxide dismutase (<em>SOD</em>), catalase (CAT) and glutathione peroxidase (GPx) and non-enzymatic antioxidant reduced glutathione (GSH) content and levels of Lipid peroxidation (LPO) in gill, liver, brain and intestine of juvenile carp (Cyprinus carpio) were evaluated after exposure to different concentrations (0.5, 5.0 and 50.0mg/L) of waterborne nano-ZnO for 1, <em>3</em>, 7, 10 and 14 day. The results showed that the variation trendency of antioxidant defense systems and LPO levels would be more significant with increasing concentration and exposure time. 50.0mg/L nano-ZnO caused significant decrease of several enzymes activities and GSH content and increase of LPO level. As a result, these biomarkers were all appropriate for monitoring oxidative stress status of fish after exposure to nano-ZnO. Gill, liver and brain might be more sensitive response organs, being intestine the least altered organ. Further ecotoxicological evaluation should be made concerning the risk of nano-ZnO on aquatic environment.