Reduction of the oxidative damage to H_(2)O_(2)-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside

Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.

Roles of Aqueous Extract of Marigold on Arsenic-Induced Oxidative Damage in Pancreatic Islet β-Cells

Roles of Marigold extracts (ME) on arsenic trioxide (ATO)-induced oxidative damage to pancreatic β-cells need to be further elucidated. In this study, NIT-1 cells were treated with different concentrations of and/or ATO, following by the cell viability was detected by CCK8 assay. Then, intracellular reactive oxygen species (ROS) levels, lipid peroxide (MDA) contents and superoxide dismutase (SOD) activity were measured with a fluorescence probe method and colorimetric assay, respectively. The apoptosis rate and morphology was detected and observed with hoechst 33,258 staining assay. The mRNA levels and protein expressions of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were measured by real-time fluorescence quantitative polymerase chain reaction and protein immunoblotting assay, respectively. Our results indicated that Co-treatment with ME and ATO exacerbated the cell viability decreasing reduced by ATO, while the addition of ME after ATO treatment effectively promote the recovery of ATO reduced survival rates. The ATO group increased apoptosis (P P β-cells by modulating the activation of the Nrf2 signaling pathway.

Abnormal Reactions of Free Radicals and Oxidative Damages in the Bodies of Patients With Chronic Glomerulonephritis

Objective To study the abnormal reactions of a series of free radicals and the oxidative damages induced by free radical abnormal reactions in the bodies of patients with chronic glomerulonephritis. Methods Eighty chronic glomerulonephritis patients (CGNP) and eighty healthy adult volunteers (HAV) were enrolled in a random control study, in which concentrations of nitric oxide (NO) in plasma, lipoperoxides (LPO) in plasma and in erythrocytes, and vitamin C (VC), vitamin E (VE) and beta-carotene (?CAR) in plasma as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric assays. Results Compared with the average values of the above biochemical parameters in the HAV group, the average values of NO in plasma, and LPO in plasma and erythrocytes in the CGNP group were significantly increased (P = 0.0001), while those of VC, VE and -CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the CGNP group were significantly decreased (P = 0.0001). Pearson product-moment correlation analysis showed that with increase of the concentration of blood creatinine as well as prolongation of the course of disease in the CGNP, the concentrations of NO in plasma, and LPO in plasma and erythrocytes in the CGNP increased gradually, while the concentrations of VC, VE and ?CAR in plasma as well as the activities of SOD, CAT and GPX in erythrocytes in the CGNP decreased gradually (P = 0.002454 0.000001). The relative risk ratio (RR) of the above biochemical parameters reflecting oxidative damages in the bodies of CGNP ranged from 6.061 to 72.429. The reliability coefficient (alpha) that the above biochemical parameters were used to reflect the oxidative damages of the CGNP was 0.8137, standardized item alpha = 0.9728, Hotelling抯 T-Squared = 1135680.191, F = 53274.6478, P = 0.000001. Conclusions The findings in this study show that in the bodies of CGNP a series of free radical chain reactions result in severe pathological aggravation and induce oxidative damages in their bodies. Therefore, suitable dose of antioxidants should be supplemented to them so as to alleviate oxidative damages in their bodies.

Increased oxidative stress and oxidative damage associated with chronic bacterial prostatitis

Aim： To investigate whether chronic bacterial prostatitis might increase oxidative stress and oxidative damage in chronic bacterial prostatitis patients （CBPP）, and to explore its possible mechanism. Methods： Enrolled in a casecontrol study were 70 randomly sampled CBPP and 70 randomly sampled healthy adult volunteers （HAV）, on whom plasma nitric oxide （NO）, vitamin C （VC）, vitamin E （VE） and β-carotene （β-CAR） level, erythrocyte malondialdehyde （MDA） level, as well as erythrocyte superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GPX） activities were determined by spectrophotometry. Results： Compared with the HAV group, values of plasma NO and erythrocyte MDA in the CBPP group were significantly increased （P 〈 0.001）; those of plasma VC, VE and β-CAR as well as erythrocyte SOD, CAT and GPX activities in the CBPP group were significantly decreased （P 〈 0.001）. Findings from partial correlation for the 70 CBPP showed that with prolonged course of disease, values of NO and MDA were gradually increased （P 〈 0.001）, and those of VC, VE, β-CAR, SOD, CAT and GPX were gradually decreased （P 〈 0.05- 0.001）. The findings from stepwise regression for the 70 CBPP suggested that the model was Y= -13.2077 ＋ 0.1894MDA ＋ 0.0415NO - 0.1999GPX, F = 18.2047, P 〈 0.001, r = 0.6729, P 〈 0.001. Conclusion： The findings suggest that there exist increased oxidative stress and oxidative damage induced by chronic bacterial prostatitis in the patients, and such phenomenon was closely related to the course of disease.

Dietary resveratrol attenuation of intestinal inflammation and oxidative damage is linked to the alteration of gut microbiota and butyrate in piglets challenged with deoxynivalenol

Background:Deoxynivalenol(DON)is a widespread mycotoxin that induces intestinal inflammation and oxidative stress in humans and animals.Resveratrol(RES)effectively exerts anti-inflammatory and antioxidant effects.However,the protective effects of RES on alleviating DON toxicity in piglets and the underlying mechanism remain unclear.Therefore,this study aimed to investigate the effect of RES on growth performance,gut health and the gut microbiota in DON-challenged piglets.A total of 64 weaned piglets[Duroc×(Landrace×Yorkshire),21-d-old,6.97±0.10 kg body weight(BW)]were randomly allocated to 4 treatment groups(8 replicate pens per treatment,each pen containing 2 males;n=16 per treatment)for 28 d.The piglets were fed a control diet(CON)or the CON diet supplemented with 300 mg RES/kg diet(RES group),3.8 mg DON/kg diet(DON)or both(DON+RES)in a 2×2 factorial design.Results:DON-challenged piglets fed the RES-supplemented diet had significantly decreased D-lactate concentrations and tumor necrosis factor alpha(TNF-α)and interleukin 1 beta(IL-1β)mRNA and protein expression,and increased zonula occludens-1(ZO-1)mRNA and protein expression compared with those of DON-challenged piglets fed the unsupplemented diet(P<0.05).Compared with unsupplemented DON-challenged piglets,infected piglets fed a diet with RES showed significantly decreased malondialdehyde(MDA)levelsand increased mRNA expression of antioxidant enzymes and antioxidant genes(i.e.,GCLC,GCLM,HO-1,SOD1 and NQO-1)and glutamatecysteine-ligase modulatory subunit(GCLM)protein expression(P<0.05).Moreover,RES supplementation significantly abrogated the increase in the proportion of TUNEL-positive cells and the protein expression of caspase3 in DON-challenged piglets(P<0.05).Finally,RES supplementation significantly increased the abundance of Roseburia and butyrate concentrations,while decreasing the abundances of Bacteroides and unidentified-Enterobacteriaceae in DON-challenged piglets compared with DON-challenged piglets alone(P<0.05).Conclusions:RES supplementation improved gut health in DON-challenged piglets by strengthening intestinal barrier function,alleviating intestinal inflammation and oxidative damage,and positively modulating the gut microbiota.The protective effects of RES on gut health may be linked to increased Roseburia and butyrate concentrations,and decreased levels of Bacteroides and unidentified-Enterobacteriaceae.

Ozone Emitted During Copying Process-A Potential Cause of Pathological Oxidative Stress and Potential Oxidative Damage in the Bodies of Operators

To estimate the impact of copying on the indoor air quality, and to investigate whether ozone emitted during such a process induces pathological oxidative stress and potential oxidative damage in the bodies of operators. Methods 67 copying operators (CO) and 67 healthy volunteers (HV) were enrolled in a random control study, in which levels of lipoperoxide (LPO) in plasma and erythrocytes, and levels of vitamin C (VC), vitamin E (VE) and b-carotene (b-CAR) in plasma as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined by spectrophotometric methods. Results Compared with the HV group, the average values of LPO in plasma and erythrocytes in the CO group were significantly increased (P<0.0001), while those of VC, VE and b-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the CO group were significantly decreased (P<0.0001). Pearson product-moment correlation analysis showed that with increase of ozone level in copying sites and duration of exposure to ozone, the values of LPO in plasma and erythrocytes in the bodies of operators were gradually increased,while those of VC, VE, b-CAR, SOD, CAT and GPX were decreased in the same manner. Odds ratio (OR) of risk of biochemical parameters reflecting potential oxidative damage of the copying operators ranged from 4.440 to 13.516, and 95 % CI of OR was from 2.113 to 34.061. Reliability coefficient () of the biochemical parameters used to reflect the potential oxidative damage of the operators was 0.8156, standardized item =0.9929, P<0.0001. Conclusion Findings in the present study suggest that there exist a series of free radical chain reactions and pathological oxidative stress induced by high dose ozone in the operators, thereby causing potential oxidative and lipoperoxidative damages in their bodies.

Effect of methylmercury on some neurotransmitters and oxidative damage of rats

In order to study the molecular mechanism of injury in rat organs induced by methylmercury, and the relationship between neurotransmitter and oxidative damage in the toxicity process of rat injury by methylmercury was studied. The control group was physiological saline of 0.9%, the concentration of exposure groups were 5 mg/(kg5d) and 10 mg/(kg5d) respectively. The content of AChE, ACh, NOS, NO, MDA, SOD, GSH-Px and GSH in different organs of rats were determined with conventional methods. The results showed that after exposure to methylmercury for 7 d, the mercury content in brain of exposure groups increased clearly and had significant difference compared with the control group(P<0.01). In rat's brain, serum, liver and kidney, the content of ACh and AChE were all decreased; the content of NOS and NO were all increased; the content of MDA was increased compared with the control group, the exposure groups had significant difference (P<0.01); the content of SOD, GSH and GSH-Px was decreased compared with the control group, the exposure groups had significant difference(P<0.01). It could be concluded that methylmercury did effect the change of neurotransmitter and free radical. They participated in the toxicity process of injury by methylmercury. The damage of neurotransmitter maybe cause the chaos of free radical and the chaos of free radical may also do more damage to neurotransmitter vice versa.

Putrescine Plays a Positive Role in Salt-Tolerance Mechanisms by Reducing Oxidative Damage in Roots of Vegetable Soybean

Polyamines play important roles in plant tolerance to environmental stress. With the aim of investigating the possible involvement of putrescine （Put） in salt-tolerance mechanisms in vegetable soybean roots, exogenous Put （10 mmol L＂） and its biosynthetic inhibitor D-arginine （D-Arg） （0.5 mmol L-1） were added to nutrient solution when vegetable soybean （Glycine max L. cv. Huning 95-1） seedlings were exposed to 100 mmol L^-11 sodium chloride （NaCl）. The results showed that Put ameliorated but D-Arg aggravated the detrimental effects of NaCl on plant growth and biomass production. Under NaCl stress, levels of free, soluble conjugated and insoluble bound types of Put in roots of vegetable soybean were reduced, whereas those of free, soluble conjugated, and insoluble bound types of spermidine （Spd） and spermine （Spm） were increased. Exogenous Put eliminated the decrease in Put but promoted the increase of Spd and Spm. However, these changes could be reversed by D-Arg. Under NaCl stress, activities of arginine decarboxylase （ADC）, S-adenosylmethionine decarboxylase （SAMDC）, diamine oxidase （DAO）, and polyamine oxidase （PAO） were induced, with exogenous Put promoting and D-Arg reversing these changes. Furthermore, NaCl stress decreased activities of antioxidant enzymes. Exogenous Put alleviated but D-Arg exaggerated these effects of NaCl stress, resulting in the same changes in membrane damage and reactive oxygen species （ROS） production. These results indicated that Put plays a positive role in vegetable soybean roots by activating antioxidant enzymes and thereby attenuating oxidative damage.

Oxidative Damage to Lung Tissue and Peripheral Blood in Endotracheal PM_(2.5)-treated Rats

Objective To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats. Methods PM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase （GSH-Px） and concentration of malondialdehyde （MDA） were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length （μm） and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. Results The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length （μm） and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. Conclusion PM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length （μm） and rate of tail are simple and valuable biomarkers of PM2 5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.

Oxidative damage of primary cultured hippocampal neurons Does androgen have an antagonistic effect?

BACKGROUND： Evidence illustrates that androgen has a neuroprotective role. However, whether androgen also has the protective effect on hippocampal neurons during free radical mediated injury remains unclear. OBJECTIVE： To investigate the neuroprotective effect of androgen on hippocampal neurons during free radical damage. DESIGN, TIME AND SETTING： A controlled in vitro experiment was performed at the Department of Human Anatomy, Cell Culture Lab, and Neuroendocrinology Lab, Basic Medical School, Hebei Medical University from February to June 2009. MATERIALS： Testosterone was provided by Tianjin Jinyao Amino Acid Company, China. METHODS： Primary cultured neurons from 24 Sprague Dawley rats were randomly assigned into four groups： control, H202, testosterone, and testosterone （pre-added） plus H2O2 groups. MAIN OUTCOME MEASURES： The positive cell ratio of microtubule associated protein-Ⅱ and neuron specific enolase was determined by immunocytochemistry. Neuronal morphology was observed by hematoxylin-eosin staining and Nissl staining. Cell vitality and viability were determined using an inverted phase contrast microscope. The content of nitric oxide synthase, malondialdehyde, and superoxide dismutase were measured with a spectrophotometer. RESULTS： As compared with the control group, cell vitality and viability, and superoxide dismutase level were significantly decreased in the H202 group （P 〈 0.05）, while nitric oxide synthase and malondialdehyde levels were significantly increased （P 〈 0.05）. Neuronal vitality and viability as well as superoxide dismutase level in the testosterone plus H2O2 group were significantly greater than in the H2O2 group （P 〈 0.05）, and nitric oxide synthase and malondialdehyde levels were significantly less than in the H2O2 group （P〈 0.05）. CONCLUSION： Androgen partially reversed H2O2-induced neuronal damage and protected neurons.

Oxidative Damage to Spodoptera fitura Cell Induced byα-Terthienyl

In this study, the oxidative damage of α-terthienyl （α-T） to the Spodoptera litura （SL） cell and its mechanism were investigated. MTT was used to compare the toxicity of α-T and rotenone to the SL cell. The output of malondialdehyde and relative content of glutathione were determined with 2-thiobarbituric acid （TBA） and 5, 5＇-dithio-bis （2-nitrobenzoic acid） （DTNB）, respectively. Transmission electron microscope （TEM） was employed to observe the influence of α-T on the membrane and organelle of the SL cell. The result showed that the IC50 value of α-T to the SL cell was 0.21 μg mL^-1, whereas the corresponding dose of rotenone was 12.25 μg mL^-1. The output of MDA had the same changing tendency with the concentration of α-T, whereas the content of GSH had the negative correlation with it. According to TEM, the cell membrane and karyotheca swelled and couldn＇t retain integrity, the intracellular substances leaked out, unidentified granules appeared in the SL cell. The mitochondria expanded, and the membrane and subcellular organelle were damaged severely. In this study, it was found that after oxidative damage induced by α-T, the output of MDA increased notably, whereas the relative content of GSH decreased. This indicated that the antioxidant ability of cell weakened. The result of TEM implied that the SL cell suffered from oxidative damage under the appointed dose.

Cellular Oxidative Damage of HEK293T Cells Induced by Combination of CdCl_2 and Nano-TiO_2

This study investigated the conjoined cellular oxidative damage of human embryo kidney 293T（HEK293T） cells induced by cadmium chloride（CdCl2） and nanometer titanium dioxide（nano-TiO2）.RT-PCR technique was used to detect the expressions of Heme oxygenase-1（HO-1） and 8-oxoguanine DNA glycosylase（OGG1）.The activities of superoxide dismutase（SOD） and catalase enzyme（CAT） and concentrations of reactive oxygen species（ROS） and maldondialdehyde（MDA） were measured by different approaches.The results showed that CdCl2 and nano-TiO2 at a low concen-tration of 0.75 total toxic unit（TU） exerted an additive effects on HO-1 gene expression,CAT activities and MDA concentrations.When the total TU was increased to 1 or 1.25 TU,the interaction was syner-getic.Moreover,the mixture with high proportion of CdCl2 produced an additive effect on the OGG1 gene expression,and the interaction was changed to be synergetic when the concentration of CdCl2 was lower than or equal to that of nano-TiO2.Synergetic effects of CdCl2 and nano-TiO2 on cellular oxida-tive damage of HEK293T cells were found as indicated by the changes in the SOD activities and ROS concentrations.It was concluded that CdCl2 and nano-TiO2 exerts synergistic effects on the cellular oxidative damage of HEK293T cells,and the sensitivity of these indicators of oxidative damage varies with the proportion of CdCl2 and nano-TiO2 in the mixture.

Striatal oxidative damages and neuroinflammation correlate with progression and survival of Lewy body and Alzheimer diseases

Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas.The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated.In this observational study,we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases(LBDs)and Alzheimer disease(AD),shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration.We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival.Disease progression in LBDs correlated positively with poly(ADP-Ribose)and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts,indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes.Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxo-d G)and myeloperoxidase concentrations in the striatum,suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism ofβ-amyloid entering the mitochondria and subsequent free radicals generation.Patients with lower striatal 8-oxo-d G and myeloperoxidase levels had a survival advantage in AD.The age of onset also affected disease progression.Tissue requests for the postmortem biochemistry,genetics,and autoradiography studies were approved by the Washington University Alzheimer's Disease Research Center(ADRC)Biospecimens Committee(ethics approval reference number:T1705,approval date:August 6,2019).Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health&Safety Biological Safety Committee(approval code:3739,approval date:February 25,2020).Radioactive Material Authorization was approved by the Washington University Environmental Health&Safety Radiation Safety Committee(approval code:1056,approval date:September 18,2019).

Depression and oxidative damage in TNM stage Ⅲ patients with poorly differentiated gastric adenocarcinoma

Objective To investigate the association between psychological stress and oxidative damage in TNM stage Ⅲ patients with poorly differentiated gastric adenocarcinoma (GA). Methods One hundred and six patients with newly diagnosed poorly differentiated GA were assessed using the Hamilton Depression Rating Scale (HAMD), Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Symptom Checklist 90 (SCL-90), activities of daily living (ADL) and other multiple-item questionnaires. Oxidative-stress-related parameters in serum and the expression of DNA repair genes were monitored during a pretreatment period. Results The patients were divided into depression and nondepression groups (Groups A and B, respectively) based on a HAMD score cutoff of 20. The mean SDS, SAS, SCL-90, ADL and passive coping scores were higher in Group A, whereas social support and quality of life were lower. Serum total antioxidant capacity, catalase, superoxide dismutase concentrations and anti-superoxide anion capacity (A-ASC) were significantly decreased in Group A, whereas serum malondialdehyde (MDA) and 8-hydroxy-deoxyguanosine (8-OHdG) levels were significantly increased. Pearson correlation analysis revealed that depression was positively correlated with MDA, SAS, SCL-90 and ADL, but negatively correlated with A-ASC. Furthermore, real-time PCR revealed that the expression levels of hOGG1 and APEX1 were increased in Group A. Conclusion Psychological stress might be related to impaired antioxidant system in patients with GA, and it presents the first evidence of the involvement of oxidative DNA damage in the pathogenesis of depression.

Increased systemic RNA oxidative damage and diagnostic value of RNA oxidative metabolites during Shigella flexneri-induced intestinal infection

BACKGROUND Shigella flexneri(S.flexneri)is a major pathogen causing acute intestinal infection,but the systematic oxidative damage incurred during the course of infection has not been investigated.AIM To investigate the incurred systemic RNA oxidative damage and the diagnostic value of RNA oxidative metabolites during S.flexneri-induced intestinal infection.METHODS In this study,a Sprague-Dawley rat model of acute intestinal infection was established by oral gavage with S.flexneri strains.The changes in white blood cells(WBCs)and cytokine levels in blood and the inflammatory response in the colon were investigated.We also detected the RNA and DNA oxidation in urine and tissues.RESULTS S.flexneri infection induced an increase in WBCs,C-reactive protein,interleukin(IL)-6,IL-10,IL-1β,IL-4,IL-17a,IL-10,and tumor necrosis factorα(TNF-α)in blood.Of note,a significant increase in urinary 8-oxo-7,8-dihydroguanosine(8-oxo-Gsn),an important marker of total RNA oxidation,was detected after intestinal infection(P=0.03).The urinary 8-oxo-Gsn level returned to the baseline level after recovery from infection.In addition,the results of a correlation analysis showed that urinary 8-oxo-Gsn was positively correlated with the WBC count and the cytokines IL-6,TNF-α,IL-10,IL-1β,and IL-17α.Further detection of the oxidation in different tissues showed that S.flexneri infection induced RNA oxidative damage in the colon,ileum,liver,spleen,and brain.CONCLUSION Acute infection induced by S.flexneri causes increased RNA oxidative damage in various tissues(liver,spleen,and brain)and an increase of 8-oxo-Gsn,a urinary metabolite.Urinary 8-oxo-Gsn may be useful as a biomarker for evaluating the severity and prognosis of infection.

Midazolam Impairs Learning and Memory Ability Through ERK/CREB Signaling Pathway and Oxidative Damage of Hippocampus in Rats

This study aimed to elucidate whether midazolam affected the learning and memory of rats through the extracellular signal-regulated kinase(ERK)/cyclic adenosine monophosphate response element-binding(CREB)signaling pathway and hippocampal oxidative damage.Overall 120 Wistar rats were randomly assigned to four groups,including one control and three midazolam-exposed groups(20,60 and 150 mg•kg^(-1)).After an intraperitoneal injection of midazolam/physiological saline for both 1 h(n=15)and 24 h(n=15),10 rats(five came from 1 h,and the remaining five came from 24 h)were randomly selected from each group for the Morris water maze test.The hippocampus tissue samples were harvested for the assessment of superoxide dismutase(SOD)and catalase(CAT)activities as well as glutathione peroxidase(GPx),malonyl dialdehyde(MDA),nitric oxide(NO)and inducible nitric oxide synthase(iNOS)levels.The remaining 80 rats were euthanized,and the hippocampal tissue was isolated.The expressions of ERK1,ERK2 and CREB mRNA were tested using RT-qPCR.The protein expressions of p-ERK1/2 and p-CREB were tested using Western blotting.The Morris water maze tests indicated that midazolam-treated rats have weaker learning and memory ability compared to the control rats.Midazolam increased MDA,NO,iNOS and CAT,and decreased GPx and SOD activities compared to the control group.The expression levels of ERK1/2 and CREB in the hippocampus of rats in the midazolam treatment groups were significantly lower compared to the control group at 1 h after intraperitoneal injection of midazolam,and in a dose-dependent relationship but returning it to normal levels at 24 h after midazolam intraperitoneal injection.Therefore,it was concluded that the learning and memory impairment of midazolam might be associated with the down-regulation of the ERK/CREB signaling pathway and oxidative damage in rat hippocampus.

An exploration on the protective mechanism of Xuduan Zhongzi prescription against epididymis oxidative damage in oligoasthenospermia model rats based on Nrf2-NQO1/γ-GCS signaling pathway

Objective:To investigate the protective mechanism of Xuduan Zhongzi prescription against epididymal oxidative damage in oligoasthenospermia model rats.Methods:Forty SD rats were randomly divided into blank group,model group,Xuduan Zhongzi prescription group(10g/kg)and L-carnitine group(0.1g/kg).Except blank group,all induced oligoasmospermia.The blank group and model group were given normal saline intragastric administration,the Xuduan Zhongzi prescription group was given Xuduan Zhongzi prescription solution intragastric administration,and the L-carnitine group was given L-carnitine intragastric administration.HE staining was used to observe the epididymis structure after 8 weeks.The concentration and activity rate of epididymis sperm were measured by sperm quality.MRNA and protein expression levels of Nrf2,NQO1 andγ-GCs in epididymis were detected by RT-qPCR and immunohistochemistry.Results:①HE staining:in the blank group,the epididymis tubes were arranged tightly and regularly,the tissue structure was complete,the epithelial cells were arranged orderly,and the lumen sperm were numerous and evenly distributed.The epididymis of model group showed structural atrophy,loose arrangement,enlarged mesenchyme,increased cell debris and significantly reduced sperm cells.Compared with the model group,the lumen lesions of epididymis in Xuduan Zhongzi prescription group and L-carnitine group were significantly improved,and the amount of normal sperm in lumen was increased and the distribution was uniform.②Results of sperm quality comparison among each group:sperm density and sperm motility rate:compared with blank group,sperm density and sperm motility rate in other groups were significantly decreased(P<0.05),and sperm density and sperm motility rate in model group were significantly decreased(P<0.05);Compared with model group,the sperm density and motility rate in Xuduan Zhongzi prescription group and L-carnitine group were significantly increased(P<0.05).③RT-qPCR and immunohistochemistry:Compared with the blank group,the mRNA and protein levels of Nrf2,NQO1 andγ-GCs in epididymal rats in model group were significantly decreased(P<0.05),while the mRNA and protein levels of Nrf2,NQO1 andγ-GCs were significantly increased in L-carnitine group and Continua seed formula group(P<0.05).Conclusion:Xuduan Zhongzi prescription can reduce oxidative stress damage and improve sperm quality of oligoasthenospermia.The mechanism may related to promoting the activation of Nrf2-NQO1/γ-GCS pathway in epididymis of oligoasthenospermia rats,and up-regulate the expressions of Nrf2,NQO1 andγ-GCS proteins.

DNA and RNA oxidative damage in hepatocellular carcinoma patients and mortality during the first year of liver transplantation

BACKGROUND Oxidative damage of DNA and RNA has been associated with mortality of patients with different diseases.However,there is no published data on the potential use of DNA and RNA oxidative damage to predict the prognosis of patients with hepatocellular carcinoma(HCC)undergoing liver transplantation(LT).AIM To determine whether patients with increased DNA and RNA oxidative damage prior to LT for HCC have a poor LT prognosis.METHODS Patients with HCC who underwent LT were included in this observational and retrospective study.Serum levels of all three oxidized guanine species(OGS)were measured prior to LT since guanine is the nucleobase that forms DNA and RNA most prone to oxidation.LT mortality at 1 year was the end-point study.RESULTS Surviving patients(n=101)showed lower serum OGS levels(P=0.01)and lower age of the liver donor(P=0.03)than non-surviving patients(n=13).An association between serum OGS levels prior to LT and 1-year LT(odds ratio=2.079;95%confidence interval=1.356-3.189;P=0.001)was found in the logistic regression analysis.CONCLUSION The main new finding was that high serum OGS concentration prior to LT was associated with the mortality 1 year after LT in HCC patients.

Oxidative damage of chronic PM2.5 exposure to rat lung tissue

Objective:To investigate the oxidative damage caused by chronic exposure to PM2.5 in rat lung tissues according to the PM2.5 concentration in the atmospheric environment.Methods:Forty healthy SD rats were randomly divided into 4 groups,the control group and the 5 mg/kg,10 mg/kg,20 mg/kg PM2.5 exposure groups.The rats in each group were administered by intratracheal instillation with 1ml/kg,2 times per week.After 8 weeks of exposure,the changes of lung histopathology,superoxide dismutase(SOD),malondialdehyde(MDA),catalase(CAT)and reduced glutathione/oxidized glutathione(GSH/GSSG)were detected.Results:Compared with the control group,the histopathological changes in the lung tissue of the three dose groups exposed to PM2.5 were significant.Masson staining showed obvious collagen fibrosis.The activities of SOD and CAT in the lung tissue of the exposed group were decreased,and the contents of MDA were increased with statistically significant(P<0.05),showing that the difference was the most obvious in the middle-dose group.The GSH/GSSG ratio in the lung tissue decreased,indicating that the degree of oxidative damage was aggravated.Conclusion:Chronic exposure to PM2.5 could induce oxidative stress in the lung tissue of rats and caused different degrees of oxidative damage.