Pro-oxidative and anti-oxidative imbalance in human semen and its relation with male fertility

Oxidative stress is a common condition suffered by biological systems in aerobic conditions. Human semen also has its own molecular guard against the free radicals created by normal respiratory process or from immune reactions. The equilibrium of the creation and scavenging of free radicals is mandatory in the spermatozoa to fertilize and initiate a full-term pregnancy. The paper is a systematic review of publications that evaluate oxidative stress in semen. The Cochrane Library, Medline (1966-2003), Embase (1988-2003), SciSearch (1981-2003) and the conference papers were searched. When sperm samples from fertile and infertile males were analyzed, some of the mechanisms that determine the oxidative stress level were found to be impaired while others were unaltered. In conclusion, the literature as a whole provides contradictory findings and it is necessary to carry out more work to identify all the enzymatic and non-enzymatic systems involved in oxidative stress in the ejaculate, in order to develop new diagnostic systems and therapeutic strategies for combating detrimental free radical imbalance in the semen.

Anti-oxidative stress treatment and current clinical trials

Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological process.It plays an important role in the development and progression of many chronic diseases.Upon exposure to oxidative stress or the inducers of ROS,the cellular nucleus undergoes some biological processes via different signaling pathways,such as stress adaption through the forkhead box O signaling pathway,inflammatory response through the IκB kinase/nuclear factor-κB signaling pathway,hypoxic response via the hypoxia-inducible factor/prolyl hydroxylase domain proteins pathway,DNA repair or apoptosis through the p53 signaling pathway,and antioxidant response through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 signaling pathway.These processes are involved in many diseases.Therefore,oxidative stress has gained more attraction as a targeting process for disease treatment.Meanwhile,anti-oxidative stress agents have been widely explored in pre-clinical trials.However,only limited clinical trials are performed to evaluate the efficacy of anti-oxidative stress agents or antioxidants in diseases.In this letter,we further discuss the current clinical trials related to anti-oxidative stress treatment in different diseases.More pre-clinical studies and clinical trials are expected to use anti-oxidative stress strategies as disease treatment or dietary supplementation to improve disease treatment outcomes.

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

Anti-Oxidative Constituents of Ethanol Extract from Buckwheat Seeds by HPLC-Electro-Spray MS

The study investigates major anti-oxidative constituents of ethanol extracts from the seeds of common buckwheat and tartary buckwheat. Ethanol extracts from buckwheat seeds were arranged to react with 1,1-diphenyl-2-picrylhydrazyl （DPPH） free radical. HPLC was used to identify anti-oxidative constituents of the ethanol extracts, and electro-spray MS was used to characterize the structures of these identified anti-oxidative constituents to confirm them. The ethanol extracts of common buckwheat and tartary buckwheat seeds both had DPPH free radical-scavenging effect; HPLC analysis showed that the ethanol extracts of both common buckwheat and tartary buckwheat seeds presented two main anti-oxidation peaks, which correspondingly had same chromatographic retention times and spectral information; electro-spray MS analysis showed that the molecular weights and MS fragmentation patterns of the anti-oxidative constituents in the ethanol extracts from buckwheat seeds were the same as those of rutin and quercetin in the control samples. HPLC- MS/MS was capable of being used to rapidly identify anti-oxidative constituents in the extract of buckwheat seeds, and the main anti-oxidative constituents of buckwheat seed extract were mainly rutin and quercetin, and the anti-oxidative activity of quercetin was higher than that of rutin.

A Study on Anti-oxidative Activity of Soybean Peptideswith Linoleic Acid Peroxidation Systems

Soybean bioactive peptides（SBPs） were prepared from the isolated soybean protein by proteolysis with an alkaline protease, alcalase, at 50℃ and pH = 8.0. The dependence of hydrolysis time on hydrolysis degree and molecular weight distribution were examined. The hydrolysate was fractionated on a Sephadex G-25 column and the anti-oxidative activities of the fractions were detected by the method of pyrogallol auto-oxidation. The average chain length of soybean peptides that have anti-oxidative activity was estimated to be about 7. The anti-oxidative properties of the soy- bean peptide were also studied by using linoleic acid peroxidation systems. The optimal condition of the peroxidation system was set up, Vc/Cu^2 ＋ as the inducer at pH = 7.4 and 25 ℃. In addition, soybean peptides show higher antioxidative activity compared with GSH.

Inhibitive effects of anti-oxidative vitamins on mannitol-induced apoptosis of vascular endothelial cells

Objective: Study blood vessel injury and gene expression indicating vascular endothelial cell apoptosis induced by mannitol with and without administration of anti-oxidative vitamins. Methods: Healthy rabbits were randomly divided into four groups. Mannitol was injected into the vein of the rabbit ear in each animal. Pre-treatment prior to mannitol injection was per- formed with normal saline (group B), vitamin C (group C) and vitamin E (group D). Blood vessel injury was assessed under electron and light microscopy. In a second experiment, cell culture specimen of human umbilical vein endothelial cells were treated with mannitol. Pre-treatment was done with normal saline (sample B), vitamin C (sample C) and vitamin E (sample D). Total RNA was extracted with the original single step procedure, followed by hybridisation and analysis of gene expression. Results: In the animal experiment, serious blood vessel injury was seen in group A and group B. Group D showed light injury only, and normal tissue without pathological changes was seen in group C. Of all 330 apoptosis-related genes analysed in human cell culture specimen, no significant difference was seen after pre-treatment with normal saline, compared with the gene chip without pre-treatment. On the gene chip pre-treated with vitamin C, 45 apoptosis genes were down-regulated and 34 anti-apoptosis genes were up-regulated. Pre-treatment with vitamin E resulted in the down-regulation of 3 apoptosis genes. Conclusion: Vitamin C can protect vascular endothelial cells from mannitol-induced injury.

Pretreatment with Rhodiola Rosea Extract Reduces Cognitive Impairment Induced by Intracerebroventricular Streptozotocin in Rats: Implication of Anti-oxidative and Neuroprotective Effects

Objective To investigate the pretreatment effects of Rhodiola rosea （R. rosea） extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer＇s disease （AD）. Methods Male Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin （1.5 mg/kg） on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde （MDA）, glutathione reductase （GR） and reduced glutathione （GSH） levels in hippocampus and histopathology of hippocampal neurons. Results The MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract （3.0 g/kg）. Conclusion R. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.

Reducing Dietary Cation-Anion Difference on Acid-Base Balance, Plasma Minerals Level and Anti-Oxidative Stress of Female Goats

Reducing dietary cation-anion difference （DCAD） has been proved an effective way to prevent milk fever in dairy cows. Based on the similar physiological gastro-intestinal tract anatomy and metabolic process between female goats and dairy cows, this study was conducted to evaluate the effects of varying DCAD on fluid acid-base status, plasma minerals concentration and anti-oxidative stress capacity of female goats. Urinary pH, plasma Ca, P and Mg; and anti-oxidative stress indices of total superoxide dismutase （T-SOD）, hydrogen peroxide （HzO2）, glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） were determined to evaluate the effect. Forty-eight Guizhou black female goats （（15±1.9） mon of old, （22.3±3.75） kg of BW） were randomly allocated to 4 blocks of 12 goats each and were fed 1 of 4 diets differed in DCAD level （calculated as Na＋K-C1-S, mEq kg-1 DM）. Levels of DCAD were preliminarily designed to be control （＋ 150 mEq kg^-1 DM, CON）, high DCAD （＋300 mEq kg^-1 DM, HD）, low DCAD （0 mEq kg^-1 DM, LD） and negative DCAD （-150 mEq kg^-1 DM, ND）, respectively. A commercial anionic salts （Animate） and sodium bicarbonate （NaHCO3） were supplemented to reduce and increase DCAD level, respectively. There was no difference in dry matter intake for 4 groups of goats. Urine pH was aggressively decreased （P〈0.0001） with reduced DCAD and there was a strong association between DCAD and urine pH （R2=0.793, P〈0.0001）. Compared with CON and HD feeding of LD and ND resulted in greater （P〈0.05） plasma Ca concentration. Plasma P level was increased （P〈0.05） when anionic salts were supplemented. The DCAD alteration did not affected （P〉0.05） plasma Mg level. There was no significant （P〉0.05） difference in plasma GSH-Px activity and H202, but anionic salts supplementation in LD and ND significantly increased （P〈0.05） plasma T-SOD activity and tended to reduce MDA （P〈0.1） over HD and CON. Results from this study indicated that reducing DCAD could decrease urine pH and increase plasma Ca concentration of female goats. Additionally, reducing DCAD was helpful to enhance anti-oxidative stress capability of female goats.

Preparation and Anti-oxidative Effects of Corn Peptides

Corn peptides(CP) were prepared from zein via proteolysis by means of a type of alkaline protease, Alcalase, at 50 ℃ and pH 8.0. The anti oxidative activity of the hydrolysate was examined. It was found that the anti oxidative activity reached the maximum at the fourth hour of the hydrolysis and then decreased. The effect of the enzyme dosage on the solubility of corn protein, the dependence of hydrolysis time on the degree of the hydrolysis(DH) and molecular weight distribution were examined respectively. 30% DH was controlled on the basis of anti oxidative activity. The hydrolysate was fractionated on a Sephadex G 15 column. The anti oxidative activities were examined for all the fractions. The main fraction for anti oxidative activity was collected and characterized by the methods of amino acid analysis, the measurement of average chain length and etc .. The main M W distribution of the main fraction was 300-600 Daltons. The anti oxidative properties of the small peptides in vitro were studied. It was found that they could inhibit the auto oxidation of pyrogallol and the oxidation of hemoglobin. The hemolysis degree of erythrocyte caused by hydroxyl free radicals was decreased greatly, indicating a protective effect of the anti oxidative peptides on the cell membrane damage of erythrocyte.

Chemical analysis,antimicrobial and anti-oxidative properties of Daucus gracilis essential oil and its mechanism of action

Objective:To evaluate the essential oils(EO) composition,antimicrobial and antioxidant power of a local plant,Daucus gracilis(D.gracilis).Methods:The aerial parts of D.gracilis were subjected to hydro distillation by a Clevenger apparatus type to obtain the EO which had been analyzed by gas chromatography and gas chromatography coupled with mass spectrometry,and screened for antimicrobial activity against five bacteria and three fungi by agar diffusion method.The mechanism of action of the EO was determined on the susceptible strains by both of time kill assay and lysis experience.The minimal inhibitory concentrations were determined by agar macrodilution and micro-dilution methods.Anti-oxidative properties of the EO were also studied by free diphenyl-2-picrylhydrazyl radical scavenging and reducing power techniques.Results:The EO yielded 0.68(v/w).The chemical analysis presented two dominant constituents which were the elemicin(35.3%) and the geranyl acetate(26.8%).D.gracilis EO inhibited the growth of Bacillus cereus and Proteus mirabilis significantly with minimal inhibitory concentrations of 17.15 μg/mL by the agar dilution method and57.05 μg/mL and 114.1 μg/mL,respectively by liquid micro-dilution.A remarkable decrease in a survival rate as well as in the absorbance in 260 nm was recorded,which suggested that the cytoplasm membrane was one of the targets of the EO.The EO showed,also,important anti-oxidative effects with an IC50 of 0.002 mg/mL and a dosedependent reducing power.Conclusions:D.gracilis EO showed potent antimicrobial and anti-oxidative activities and had acted on the cytoplasm membrane.These activities could be exploited in the food industry for food preservation.

Alpha lipoic acid protects lens from H_2O_2-induced cataract by inhibiting apoptosis of lens epithelial cells and inducing activation of anti-oxidative enzymes

Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H2O2）-induced cataract.Methods:Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H2O2,0.2 mM of H2O2 plus 0.5 mM.1.0 mM.or 2.0 mM of LA for 24 h.Cataract was assessed using cross line grey scale measurement.Superoxide dismutase（SOD）.glutathione（GSH-Px）.lactate dehydrogenase（LDH）. and maloudialdehyde（MDA）activity or level in lens homogenates was measured.Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling（TUNEL） Assay.Results:A total of 0.2 mM of H2O2 induced obvious cataract formation and apoptosis in lens’ epithelial cells,but 0.5-2.0 mM of LA could block the effect of 0.2 mM H2O2 in inducing cataract and apoptosis.Furthermore.0.2 mM ol H2O2 significantly decreased SOD.GSH-Px,and LDH activity and significant increased MDA level in the lens,but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H2O2.One mM of LA was found to be the most effective. Conclusions:LA can protect lens from H2O2-induced cataract.LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.

Umbilical cord-derived mesenchymal stem cells retain immunomodulatory and anti-oxidative activities after neural induction

The immunomodulatory and anti-oxidative activities of differentiated mesenchymal stem cells contribute to their therapeutic efficacy in cell-replacement therapy. Mesenchymal stem cells were isolated from human umbilical cord and induced to differentiate with basic fibroblast growth factor, nerve growth factor, epidermal growth factor, brain-derived neurotrophic factor and forskolin. The mesenchymal stem cells became rounded with long processes and expressed the neural markers, Tujl, neurofilament 200, microtubule-associated protein-2 and neuron-specific enolase. Nestin expression was significantly reduced after neural induction. The expression of immunoregulatory and anti-oxidative genes was largely unchanged prior to and after neural induction in mesenchymal stem cells. There was no significant difference in the effects of control and induced mesenchymal stem cells on lymphocyte proliferation in co-culture experiments. However, the expression of human leukocyte antigen-G decreased significantly in induced neuron-like cells. These results suggest that growth factor-based methods enable the differentiation of mesenchymal stem cell toward immature neuronal-like cells, which retain their immunomodulatory and anti-oxidative activities.

Syringaldehyde exerts neuroprotective effect on cerebral ischemia injury in rats through anti-oxidative and anti-apoptotic properties

There are few studies on the neuroprotective effects of syringaldehyde in a rat model of cerebral ischemia. The study aimed to elucidate the mechanisms underlying the neuroprotective effects of syringaldehyde on ischemic brain cells. Rat models of cerebral ischemia were intraperitoneally administered syringaldehyde. At 6 and 24 hours after syringaldehyde administration, cell damage in the brain of cerebral ischemia rats was obviously reduced, superoxide dismutase activity and nuclear respiratory factor 1 expression in the brain tissue were markedly increased, malondi-adehyde level was obviously decreased, apoptosis-related cysteine peptidase caspase-3 and -9 immunoreactivity was obviously decreased, and neurological function was markedly improved. These ifndings suggest that syringaldehyde exerts neuroprotective effects on cerebral ischemia injury through anti-oxidation and anti-apoptosis.

Effects of Waterborne Cu and Cd on Anti-oxidative Response, Lipid Peroxidation and Heavy Metals Accumulation in Abalone Haliotis discus hannai Ino

The aim of this study was to compare the effects of waterbome copper （Cu） and cadmium （Cd） on survival, anti-oxida- tive response, lipid peroxidation and metal accumulation in abalone Haliotis discus hannai. Experimental animals （initial weight： 7.49 g±0.01 g） were exposed to graded concentrations of waterborne Cu （0.02, 0.04, 0.06, 0.08 mg L-1） or Cd （0.025, 0.05, 0.25, 0.5 mgL-1） for 28 days, respectively. Activities of the anti-oxidative enzymes （catalase, CAT; superoxide dismutase, SOD; glutathione peroxidases, GPx; glutathione S-transferase, GST）, contents of the reduced glutathione （GSH） and malondiadehyde （MDA） in the hepatopancreas, and metal accumulation in hepatopancreas and muscles were analyzed after 0, 1, 3, 6, 10, 15, 21, 28 days of metal exposure, respectively. Results showed that 0.04 mg L-1, 0.06 mg L-1 and 0.08 mgL-1 Cu caused 100% death of abalone on the 21st, 10th and 6th day, respectively. However, no dead abalone was found during the 28-day waterborne Cd exposure at all experimental concentrations. Generally, activities of SOD and GST in hepatopancreas under all Cu concentrations followed a decrease trend as the exposure time prolonged. However, these activities were firstly increased and then decreased to the control level and increased again during Cd exposure. Activities of CAT in all Cu exposure treatments were higher than those in the control. These activities were firstly increased and then decreased to the control level and increased again during Cd exposure. Contents of MDA in hepatopancreas in all Cu treatments significantly increased first and then decreased to the control level. However, the MDA contents in hepatopan- creas were not significantly changed during the 28-day Cd exposure. The metals accumulation in both hepatopancreas and muscles of abalone significantly increased with the increase of waterborne metals concentration and exposure time. These results indicated that H. discus hannai has a positive anti-oxidative defense against Cu or Cd. In conclusion, anti-oxidative mechanism in abalone to resist waterborne Cu did not follow the same pattern as that for waterborne Cd.

PREPARATION AND PROPERTIES OF BULK CERAMICS VIA PYROLYSIS OF POLYCARBOSILANE WITH ACTIVE FILLERS II.FLEXURAL STRENGTH AND ANTI-OXIDATIVE PROPERTIES OF ACTIVE FILLER/PCS DERIVED BULK CERAMICS

The flexural strengths and oxidative resistant properties of the ceramics derived from polycarbosilane and active fillers (Ti, TiH 2, TiB 2, Cr, and CrSi 2) were measured and characterized. The introduction of active fillers enhances slightly the flexural strengths, and further densification is required to obtain higher strengths. The oxidative resistant behaviors of the specimens with active fillers are, by means of weight gain in air, poorer compared with those without active fillers.

Effect of curcumin on nitric oxide synthase expression in lipopolysaccharide-activated microglia cells and the anti-oxidative effect of curcumin

BACKGROUND： It has been demonstrated that curcumin can increase the activities of various anti-oxidase in blood and tissue, effectively eliminate various free radicals, reduce the production of peroxisome, and alleviate oxidative stress reaction. Whether it has the same effect on microglia？ OBJECTIVE： To observe the effects of curcumin on the expressions of inducible nitric oxide synthase （iNOS）, nuclear factor- κ B （NF- κ B）, and superoxide dismutase （SOD） in microglial cell line BV stimulated by lipopolysaccharide （LPS）. DESIGN： An observational comparative study. SETTING： Research Room of Biochemistry, Medical College of Nantong University. MATERIALS： Mice microglia cell line BV, iNOS and NF- κ B reporter gene plasmids were presented by Dr. Bhat.NR. from the Medical University of South Carolina （USA）. Curcumin was produced by the Xi＇an Branch of China Chengdu Scholar Bio-Tech. Co.,Ltd.; LPS （E.Coli O26：B6）, anti-mice iNOS monoclonal antibody, horseradish peroxidase labeled goat-anti-mice IgG were the products of Sigma Company （USA）. METHODS： The experiments were carried out in the Research Room of Biochemistry, Medical College of Nantong University from May 2006 to April 2007. （1） Detection of iNOS： The cells were seeded onto 24-well plate at the density of 1 × 10^5, After the cells had adhered to the cover glasses, the cells were grouped as negative control group （the primary antibody was replaced by phosphate buffered solution PBS）; normal control group （the cells were normally cultured）; LPS-treated group （the cells were treated with LPS for 24 hours）; curcumin＋LPS group （the cells were treated with curcumin for 1 hour and LPS for 24 hours）. The expressions of iNOS protein were detected with immunocytochemical staining. （2） Determination of iNOS and NF- κ B gene activities： According to the introduction of the kit for transfection, iNOS or NF- κ B report gene plasmids were transiently transfected with Lipofectaminer^TM2000 liposomes into the cells in the 24-well plate for 24 hours. The cells were divided into normal control group （the cells were normally cultured after transfected with report gene plasmids）; blank plasmid group （the cells were normally cultured after transfected with blank plasmids）; LPS-treated group （the cells were treated with LPS for 4 hours after transfected with report gene plasmids）; curcumin＋LPS group （the cells were treated with curcumin for 1 hour and LPS for 24 hours after transfected with report gene plasmids）. The content of luciferase in the cell lysis buffer was determined after cell lysis. （3） Determination of SOD activity： The cells were seeded into culture bottle at the density of 1 × 10^6, and the divided into four groups, including normal control group （the cells were normally cultured）; LPS-treated group （the cells were treated with LPS for 24 hours）; curcumin＋LPS group （the cells were treated with curcumin for 1 hour and LPS for 24 hours）; vitamin C＋LPS group （the cells were treated with vitamin C for 1 hour and LPS for 24 hours）. The SOD activity was determined with xanthine oxidase and quantitative colorimetric assay. MAIN OUTCOME MEASURES： The expressions of iNOS protein, iNOS and NF- κ B, and the activity of SOD were observed. RESULTS： （1） Expression of iNOS protein in microglia： The expression of iNOS protein in the LPS-treated group was obviously higher than that in the negative control group （P 〈 0.01）; Those in the curcumin＋LPS group were significantly decreased as compared with that in the LPS-treated group （P 〈 0.01 ） （2） Expressions of iNOS and NF- κ B genes： The expressions of iNOS and NF- κ B genes in the LPS-treated group were significantly higher than those in the normal control group （P 〈 0.01）; Those in the curcumin＋LPS group were significantly lower than those in the LPS-treated group （P 〈 0.01）. （3） SOD activity： The activity of SOD in the LPS-treated group was significantly lower than those in the normal control group （P 〈 0.01）. It in the curcumin＋LPS group and vitamin C ＋LPS group was significantly higher than that in the LPS-treated group （P 〈 0.01）. CONCLUSION： Curcumin could inhibit the expression of iNOS in the activated microglia, and it also has the abilities in eliminating free radicals and antagonizing lipid peroxidation.

Therapeutic effect of Keap1-Nrf2-ARE pathway-related drugs on age-related eye diseases through anti-oxidative stress

Age-related eye diseases,including cataract,glaucoma,diabetic retinopathy(DR),and age-related macular degeneration(AMD),are the leading causes of vision loss in the world.Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye.The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body.This pathway is also active in the development of age-related eye diseases.A variety of drugs have been shown to treat agerelated eye diseases through the Keap1-Nrf2-ARE(Kelch-like ECH-Associating protein 1-nuclear factor erythroid 2 related factor 2-antioxidant response element)pathway.This review describes the role of oxidative stress in the development of age-related eye diseases,the function and regulation of the Keap1-Nrf2-ARE pathway,and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.

Prenatal exposure to the fluoride containing psychiatric drug fluoxetine and anti-oxidative alterations in the neonatal rat brain

Fluoride is a key ingredient of many psychiatric drugs like fluoxetine(Prozac■Fluoxetine■).Pregnant women frequently use this drug as they suffer from depression and anxiety disorders during this period.Fluoxetine is able to reach the fetus through the placenta and passes to the newborn through milk.In the present study,female Wistar rats were treated with 5,10,and 20 mg/L fluoxetine(containing 94% fluorides)from pregnancy day 10 to day 20.After delivery,the levels of the enzymatic antioxidants in the brain of their offspring at postnatal day 2 were measured.The results showed that,in all fluoxetine exposed groups compared with the control group,there was a significant decrease(P<0.01)in the glutathione,catalase,glutathione S-transferases and potassium and a non-significant increase(P>0.05)in the activity of malondialdehyde and creatine kinase.The results suggest that fluoxetine may be a developmental neurotoxicant due to presence of fluoride hence must be used carefully during pregnancy.

Supplementation of Yeast Extract to Practical Diet Improves the Growth, Anti-Oxidative Capacity and Intestinal Morphology of Shrimp Litopenaeus vannamei

Two control diets based on the commercial formula were designed to contain high(27%,D1)and low(22%,D2)levels of fish meal,respectively.Into D2,500,1000 and 1500 mg kg 1 of yeast extract were added,respectively,yielding three experimental diets(YE1 through YE3).Shrimp(initial body weight 0.30 g±0.02 g)were fed with the experimental diets,five tanks each diet and 30 shrimp individuals each tank,for 8 weeks,and then challenged with Vibrio parahaemolyticus.The results showed that the specific growth rate(SGR)of shrimp in D2 was significantly lower than that of shrimp in D1(P<0.05).The SGR of shrimp in YE3 was similar to that of shrimp in D1.The feed intake of shrimp was similar between D1 and D2.The feed conversion ratio and protein efficiency ratio of shrimp were similar among all diets(P>0.05).YE significantly improved the activity of glutathione S-transferase.The concentration of glutathione(GSH)and the total serum anti-oxidative capacity(T-AOC)of D1 were significantly higher than those of shrimp feeding other diets(P<0.05).The content of serum malondialdehyde of shrimp feeding YE2 and YE3 was signifi-cantly lower than that of shrimp feeding D2(P<0.05).The thickness of intestine muscular layer of shrimp feeding YE1 and YE2 was similar to that of shrimp feeding D1.The shrimp feeding YE1 showed the highest villus height of intestine among all groups.The cumulative mortality after challenging was similar among all groups(70.00%86.67%)(P>0.05).In conclusion,1000 1500 mg kg 1 of YE was suggested to be supplemented into the practical diets to improve the growth,anti-oxidative capacity and intestinal mor-phology of shrimp L.vannamei.