N-acetylcysteine and reduced glutathione reverse flupirtine-induced liver injury and pro⁃duce other beneficial effects in combination with flupirtine

OBJECTIVE To assess whether N-acetylcysteine(NAC)and reduced glutathione(GSH)are effective in reversing flupirtine-induced hepatotoxicity and whether they have other beneficial effects when combined with flupirtine.METHODS The analgesic effects of NAC and flupirtine were first evaluated in carrageenaninduced inflammatory pain and paclitaxel-induced neuropathic pain.The combination subthreshold⁃ing approach was then used to determine whether the combination of NAC and flupirtine produced synergistic analgesic effects.Hepatotoxicity markers and histopathological examination of the liver were used to assess the efficacy of NAC and GSH in reversing flupirtine-induced hepato⁃toxicity.Finally,the effect of GSH on the safe range of flupirtine was assessed in an acute tox⁃icity assay.RESULTS Flupirtine and NAC pro⁃duced dose-dependent antiallodynic effects evoked by carrageenan and paclitaxel in mice.In the above model,the combination of NAC and flupirtine produced an unexpected synergistic analgesic effect.There were no significant differ⁃ences observed in the hepatotoxicity markers and liver histopathology between the experimen⁃tal group and the control group under NAC and GSH treatment.Finally,GSH(200 mg·kg^(-1))expanded the therapeutic index of flupirtine by 1.77 times.CONCLUSION NAC and GSH are effective in preventing liver damage caused by long-term flupirtine use,which provides a solu⁃tion for the safe and effective treatment of chronic pain with flupirtine.In addition,the other benefi⁃cial effects of NAC and GSH when combined with flupirtine may provide the basis for the devel⁃opment of a new therapy with minimal sideeffects and good efficacy.

Effects of Reduced Glutathione to Centrifuged and Non-centrifuged Fresh Chilled Stallion Semen on Progressive Motility of Spermatozoa over 72 h

The aim of the current study was to evaluate the effects of supplementation of an inexpensive stallion semen extender(Next Generation■ Dr.Kenny’s with Amikacin and K-Penn)with 1 mM of the antioxidant reduced glutathione(GSH)on the progressive motility of cooled stallion semen over a period of 72 h.Both centrifuged and non-centrifuged semen samples were evaluated from six Standardbred stallions collected three times each,with one week between collections for each stallion.For centrifuged samples,non-cushioned centrifugation was done at 750 g for 10 min.All semen samples were extended to a final concentration of 50 million total cells per milliliter and stored in Equine Express II stallion semen shipping containers.Non-centrifuged samples without GSH declined from an initial mean progressive motility of 70.3%at 0 h to 9.1%at 72 h.Non-centrifuged samples with added GSH declined from an initial mean progressive motility of 70.3%at 0 h to 7.1%at 72 h.Centrifuged samples without added GSH declined from an initial mean progressive motility of 70.3%at 0 h to 46.1%at 72 h.Centrifuged samples with added GSH declined from an initial mean progressive motility of 70.3%at 0 h to 40.3%at 72 h.The results of this study did not find significant improvement in the progressive motility over time for spermatozoa prepared in a traditional skim-milk based extender with antibiotics as a result of addition of GSH to either centrifuged or non-centrifuged semen.These findings suggest that centrifugation of fresh chilled extended stallion semen may be a good idea for any semen that may be used at time points greater than 24 h after collection.

Protective Effect of Reduced Glutathione C_(60) Derivative against Hydrogen Peroxide-induced Apoptosis in HEK 293T Cells

Hydrogen peroxide（H_2O_2） and free radicals cause oxidative stress, which induces cellular injuries, metabolic dysfunction, and even cell death in various clinical abnormalities. Fullerene（C_（60）） is critical for scavenging oxygen free radicals originated from cell metabolism, and reduced glutathione（GSH） is another important endogenous antioxidant. In this study, a novel water-soluble reduced glutathione fullerene derivative（C_（60）-GSH） was successfully synthesized, and its beneficial roles in protecting against H_2O_2-induced oxidative stress and apoptosis in cultured HEK 293 T cells were investigated. Fourier Transform infrared spectroscopy and 1H nuclear magnetic resonance were used to confirm the chemical structure of C_（60）-GSH. Our results demonstrated that C_（60）-GSH prevented the reactive oxygen species（ROS）-mediated cell damage. Additionally, C_（60）-GSH pretreatment significantly attenuated H_2O_2-induced superoxide dismutase（SOD） consumption and malondialdehyde（MDA） elevation. Furthermore, C_（60）-GSH inhibited intracellular calcium mobilization, and subsequent cell apoptosis via bcl-2/bax-caspase-3 signaling pathway induced by H_2O_2 stimulation in HEK 293 T cells. Importantly, these protective effects of C_（60）-GSH were superior to those of GSH. In conclusion, these results suggested that C_（60）-GSH has potential to protect against H_2O_2-induced cell apoptosis by scavenging free radicals and maintaining intracellular calcium homeostasis without evident toxicity.

Reduced glutathione alleviates the toxic effect of 6-hydroxydopamine on bone marrow stromal cells

We studied the effect of reduced glutathione on bone marrow stromal cells （BMSCs） treated with 6-hydroxydopamine （6-OHDA）, which shows a toxic effect on dopaminergic neurons. The proliferation of BMSCs treated with 6-OHDA decreased, while that of BMSCs treated with reduced glutathione increased. The proliferation of BMSCs treated with both 6-OHDA and reduced glutathione was significantly higher compared with that treated with 6-OHDA alone. These findings indicate that reduced glutathione alleviates the toxic effect of 6-OHDA on BMSCs.

Role of Exogenous Reduced Glutathione on Time Dependent ^(203)Hg Distribution in Liver and Kidney of a Freshwater Teleost, Anabas testudineus

Time-dependent tissue distribution of mercury(Hg) was studied in a freshwater perch,Anabas testudineus which revealed that the liver and kidneys are the major sites of Hg reten tion. The role of reduced glutathione (GSH) in the clearance of Hg was also investigated to e valuate the ameliorative effect of this nucleophile. For this purpose, the perch was given GSH 15 min before or after they received 203Hg by injection. The fish were then sacrificed at 24 h and 48 h later. The results clearly indicate that exogenous GSH can significantly reduce Hg retention in both the liver and kidneys, demonstrating a direct role of this nucleophile in the amelioration of Hg-induced toxicity in the early phase of intoxication

The effect of glutathione on glucosinolate biosynthesis through the sulfur assimilation pathway in pakchoi associated with the growth conditions

Glucosinolates(GSLs) are a group of nitrogen-and sulfur-containing secondary metabolites, synthesized primarily in members of the Brassicaceae family, that play an important role in food flavor, plant antimicrobial activity, resistance to insect attack, stress tolerance, and human anti-cancer effects. As a sulfur-containing compound, glutathione has a strong connection with GSLs biosynthesis as a sulfur donor or redox system, and exists in reduced(glutathione;GSH) and oxidized(glutathione disulfide;GSSG) forms. However, the mechanism of GSH regulating GSLs biosynthesis remainds unclear. Hence, the exogenous therapy to pakchoi under normal growth condition and sulfur deficiency condition were conducted in this work to explore the relevant mechanism. The results showed that exogenous application of buthionine sulfoximine, an inhibitor of GSH synthesis, decreased the transcript levels of GSLs synthesis-related genes and transcription factors, as well as sulfur assimilation-related genes under the normal growth condition. Application of exogenous GSH inhibited the expression of GSLs synthesis-and sulfur assimilation-related genes under the normal condition, while the GSLs biosynthesis and the sulfur assimilation pathway were activated by exogenous application of GSH when the content of GSH in vivo of plants decreased owing to sulfur deficiency. Moreover,exogenous application of GSSG increased the transcript levels of GSLs synthesis-and sulfur assimilation-related genes under the normal growth condition and under sulfur deficiency. The present work provides new insights into the molecular mechanisms of GSLs biosynthesis underlying glutathione regulation.

Clinical effect of spleen aminopeptide on improving liver function damage and immune function in children with infant hepatitis syndrome

BACKGROUND Infant hepatitis syndrome(IHS)is a clinical syndrome in infants less than one year of age with generalized skin jaundice,abnormal liver function,and hepato-megaly due to various etiologies such as infection.AIM To investigate the effect of IHS patients,after treatment with arsphenamine-based peptides,on patients'liver function damage and immune function.METHODS Of 110 patients with IHS treated in our hospital from January 2019 to January 2021 were grouped according to the randomized residual grouping method,with 5 cases in each group shed due to transfer,etc.Ultimately,50 cases remained in each group.The control group was treated with reduced glutathione,and the treat-ment group was treated with sesquiterpene peptide based on the control group.Observe and compare the differences in indicators after treatment.RESULTS The comparison of serum total bilirubin,direct bilirubin,and serum alanine transferase after treatment was significantly different and lower in the treatment group than in the control group(P<0.05).The comparison of CD4+,CD3+,CD4+/CD8+after treatment was significantly different and higher in the treatment group than in the control group,and the comparison was statist-ically significant(P<0.05).The complication of the two groups showed that the rash,cough and sputum,elevated platelets,and gastrointestinal reactions in the treatment group were significantly lower than those in the control group,and the differences were statistically significant by test(P<0.05).CONCLUSION The comparative study of IHS treated with arsphenamine combined with reduced glutathione is more effective.

Antioxidation Activities of Low-Molecular-Weight Gelatin Hydrolysate Isolated from the Sea Cucumber Stichopus japonicus

Gelatin extracted from the body wall of the sea cucumber （Stichopus japonicus） was hydrolyzed with flavourzyme. Low-molecular-weight gelatin hydrolysate （LMW-GH） of 700-- 1700 Da was produced using an ultrafiltration membrane bioreaetor system. Chemiluminescence analysis revealed that LMW-GH scavenges high free radicals in a concentration-dependent manner; IC50 value for superoxide and hydroxyl radicals was 442 and 285 μgmL-1, respectively. LMW-GH exhibited excellent inhibitory characteristics against melanin synthesis and tyrosinase activity in B16 cells. Furthermore, LMW-GH notably increased in- traeellular glutathione （GSH）, which in turn suppressed melanogenesis. LMW-GH performs antioxidation activity, holding the potential of being used as a valuable ingredient in function foods, cosmetics and pharmaceuticals or nutriceuticals.

Exogenous GSH protects tomatoes against salt stress by modulating photosystem Ⅱ efficiency, absorbed light allocation and H2O2-scavenging system in chloroplasts

The effects of exogenous GSH（reduced glutathione）on photosynthetic characteristics,photosystem Ⅱ efficiency,absorbed light energy allocation and the H2O2-scavenging system in chloroplasts of salt-stressed tomato（Solanum lycopersicum L.）seedlings were studied using hydroponic experiments in a greenhouse.Application of exogenous GSH ameliorated saline-induced growth inhibition,the disturbed balance of Na＋ and Cl- ions and Na＋/K＋ ratios,and the reduction of the net photosynthetic rate（Pn）.GSH also increased the maximal photochemical efficiency of PSⅡ（Fv/Fm）,the electron transport rate（ETR）,the photochemical quenching coefficient（qP）,and the non-photochemical quenching coefficient（NPQ）.In addition,GSH application increased the photochemical quantum yield（Y（Ⅱ））and relative deviation from full balance between the photosystems（β/α-1）and decreased the PSⅡ excitation pressure（1-qP）and quantum yield of non-regulated energy dissipation（Y（NO））in leaves of salt-stressed tomatoes without BSO（L-buthionine-sulfoximine,an inhibitor of key GSH synthesis enzymeγ-glutamylcysteine synthetase）or with BSO.Further,the addition of GSH depressed the accumulation of H2O2 and malondialdehyde（MDA）,induced the redistribution of absorbed light energy in PSⅡ reaction centers,and improved the endogenous GSH content,GSH/GSSH ratio and activities of H2O2-scavenging enzymes（including superoxidase dismutase（SOD）,catalase（CAT）,peroxidase（POD）and key enzymes in the AsA-GSH cycle and Grx system）in the chloroplasts of salt-stressed plants with or without BSO.Therefore,GSH application alleviates inhibition of salt-induced growth and photosynthesis mainly by overcoming stomatal limitations,improving the PSⅡ efficiency,and balancing the uneven distribution of light energy to reduce the risk of ROS generation and to mediate chloroplast redox homeostasis and the antioxidant defense system to protect the chloroplasts from oxidative damage.Thus,GSH may be used as a potential tool for alleviating salt stress in tomato plants.

p53 antibodies,metallothioneins,and oxidative stress markers in chronic ulcerative colitis with dysplasia

AIM:To investigate the role of p53 antibodies (p53Abs),metallothioneins (MTs) and oxidative stress markers in the early detection of dysplasia in chronic ulcerative colitis (UC).METHODS:The study included 30 UC patients,15 without dysplasia (group Ⅱ) and 15 with dysplasia (group Ⅲ),in addition to 15 healthy volunteers (group Ⅰ,control subjects).The enzyme-linked immunosorbent assay technique was used to measure serum p53Abs and MTs,while advanced oxidation protein products (AOPPs),and reduced glutathione (GSH) levels were measured by spectrophotometric method in all subjects.RESULTS:In group Ⅱ and group Ⅲ compared to group Ⅰ,there were significant increases in serum levels of AOPPs (145.94 ± 29.86 μmol/L and 192.21 ± 46.71 μmol/L vs 128.95 ± 3.06 μmol/L,P < 0.002 and P <0.001,respectively),MTs (8.18 ± 0.35 μg/mL and 9.20 ± 0.58 μg/mL vs 6.12 ± 0.25 μg/mL,P < 0.05 and P < 0.05,respectively),and p53Abs (20.19 ± 3.20 U/mL and 34.66 ± 1.34 U/mL vs 9.42 ± 1.64 U/mL,P < 0.001 and P < 0.001,respectively).There were significantly higher levels of AOPPs (P < 0.05) and p53Abs (P < 0.001) in UC patients with dysplasia compared to those without dysplasia,while MTs showed no significant difference between the 2 groups (P > 0.096).In contrast,GSH levels showed a significant decrease in both patients' groups (1.87 ± 0.02 μmol/mL and 1.37 ± 0.09 μmol/mL vs 2.49 ± 0.10 μmol/mL,P < 0.05 and P < 0.05 in groups Ⅱ and Ⅲ,respectively) compared with group Ⅰ,and the levels were significantly lower in group Ⅲ than group Ⅱ (P < 0.05).There was a positive correlation between AOPPs and both MTs (r=0.678,P < 0.001) and p53Abs (r=0.547,P < 0.001),and also between p53Abs and MTs (r=0.739,P < 0.001).There was a negative correlation between AOPPs and GSH (r =-0.385,P < 0.001),and also between GSH and both MTs (r=-0.662,P < 0.001) and p53Abs (r=-0.923,P < 0.001).CONCLUSION:Oxidative stress and oxidative cellular damage play an important role in the pathogenesis of chronic UC and the associated carcinogenetic process.p53Abs levels could help in early detection of dysplasia in these conditions.

Effects of Selenium on Lipid Peroxidation and Oxidizing Ability of Rice Roots under Ferrous Stress

Water culture experiment was conducted to study the effects of selenium(Se) on glutathione peroxidase(GSH-Px) activity,reduced glutathione(GSH) concentration and the accumulation of malonaldehyde(MDA),the product of lipid peroxidation in rice seedling,as well as the effect of se on oxidizing ability of roots under ferrous stress.Results showed that appropriate amount of se significantly increased GSH-Px activity in rice leaves,F=5.5 *,enhanced the amount of GSH and oxidizing ability of roots and reduced the concentration of MDA,F=4.9 *.Compared with Se0+Fe treatment,Se treatments increased the dry matter weight of rice seedling from 10.06% to 10.43%,F=4.09 *.

Nigella sativa oil alleviates doxorubicin-induced cardiomyopathy and neurobehavioral changes in mice:In vivo and in-silico study

Objective:To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice.Methods:Swiss strain of albino female mice were divided into 6 groups of 5 animals in each:GroupⅠ(control group),groupⅡ(doxorubicin,10 mg/kg,i.v.),groupⅢ,Ⅳ,andⅤ(Nigella sativa oil;1.5,3,and 6 mL/kg,respectively),groupⅥ(Nigella sativa oil per se;6 mL/kg,p.o.).The duration of treatment was 15 d(10 days’pre-treatment and 5 days’post-treatment)and doxorubicin was administered on day 11th of the treatment schedule.Following Nigella sativa oil treatment,neurobehavioral tests,cardiac hypertrophy tests,and biochemical tests in serum and tissues were performed.Neurological tests included assessment of anxiety-like behavior in the elevated plus maze,spontaneous alternation behavior in the cross maze,and depression-like behavior in modified forced swim tests.Biochemical tests included serum lactate dehydrogenase and creatinine kinase-MB,malondialdehyde and reduced glutathione in tissues.Lastly,molecular docking was used to estimate the affinity of the phytoconstituents of Nigella sativa oil with histone deacetylases.Results:Nigella sativa oil treatment significantly(P<0.001)restored doxorubicin-induced neurobehavioral changes,decreased lactate dehydrogenase and creatinine kinase-MB in the plasma,malondialdehyde contents in tissues,and increased reduced glutathione level.Besides,no significant alteration was observed in Nigella sativa oil per se group as compared to the control.Molecular docking showed that Nigella sativa oil components had appreciable binding affinitiy with the protein cavities of HDAC1 and HDAC6.Conclusions:The result shows that Nigella sativa oil exerts anxiolytic,antidepressant,and memory-enhancing effects in addition to cardioprotective effect against doxorubicin-induced cardiomyopathy in mice.The modulatory effect of Nigella sativa oil on oxidative stress could contribute to the cardioprotective effect and associated neurobehavioral changes in mice.

Pigment epithelium-derived factor protects retinal ganglion cells from hypoxia-induced apoptosis by preventing mitochondrial dysfunction

AIM： To investigate the potential of pigment epitheliumderived factor（PEDF） to protect the immortalized rat retinal ganglion cells-5（RGC-5） exposed to Co Cl2-induced chemical hypoxia. METHODS： After being differentiated with staurosporine（SS）, RGC-5 cells were cultured in four conditions： control group cells cultured in Dulbecco ＇s modified eagle medium（DMEM） supplemented with 10% fetal bovine serum, 100 μmol/m L streptomycin and penicillin（named as normal conditions）; hypoxia group cells cultured in DMEM containing 300 μmol/m L Co Cl2; cells in the group protected by PEDF were first pretreated with 100 ng/m L PEDF for 2h and then cultured in the same condition as hypoxia group cells; and PEDF group cells that were cultured in the presence of 100 ng/m L PEDF under normal conditions. The cell viability was assessed by MTT assay, the percentage of apoptotic cells was quantified using Annexin V-FITC apoptosis kit, and intra-cellar reactive oxygen species（ROS） was measured by dichloro-dihydro-fluorescein diacetate（DCFH-DA） probe. The mitochondria-mediated apoptosis was also examined to further study the underlying mechanism of the protective effect of PEDF. The opening of mitochondrial permeability transition pores（m PTPs） and membrane potential（Δψm） were tested as cellular adenosine triphosphate（ATP） level and glutathione（GSH）. Also, the expression and distribution of Cyt C and apoptosis inducing factor（AIF） were observed.RESULTS： SS induced differentiation of RGC-5 cells resulting in elongation of their neurites and establishing contacts between outgrowths. Exposure to 300 μmol/m L Co Cl2 triggered death of 30% of the total cells in cultures within 24 h. At the same time, pretreatment with 100 ng/m L PEDF significantly suppressed the cell death induced by hypoxia（P〈0.05）. The apoptosis induced by treatment of Co Cl2 was that induced cell death accompanied with increasing intracellar ROS and decreasing GSH and ATP level. PEDF pretreatment suppressed these effects（P〈0.05）. Additionally, PEDF treatment inhibited the opening of m PTPs and suppressed decreasing of Δψm in RGC-5 cells, resulting in blocking of the mitochondrial apoptotic pathway.CONCLUSION： Pretreatment of RGC-5 cells with 100 ng/m L PEDF significantly decreases the extent of apoptosis. PEDF inhibits the opening of m PTPs and suppresses decreasing of Δψm. Moreover, PEDF also reduces ROS production and inhibits cellular ATP level＇s reduction. Cyt C and AIF activation in PEDF-pretreated cultures are also reduced. These results demonstrate the potential for PEDF to protect RGCs against hypoxic damage in vitro by preventing mitochondrial dysfunction.

Protective effect of glutamine pretreatment on ischemia-reperfusion injury of spinal cord in rabbits

Objective To investigate the effect of glutamine(Gln)on the content of reduced glutathione hormone(GSH)and aminoglutaminic acid(Glu)of spinal cord following ischemia-reperfusion injury.Methods Totally 40 healthy adult male rabbits were randomly divided into five groups:sham-operation group(S group),ischemia-reperfusion injury group(I/R group),low-dose glutamine group(L Gln group),median-dose glutamine group(M Gln group)and high-dose glutamine group(H Gln group).After glutamine preconditioning,the model of spinal cord ischemia-reperfusion injury was established according to Zivin’s method.The general status of animals was observed and the changes of Jacobs scoring were recorded in each group.Malondialdehydes(MDA),GSH,Glu and superoxide dismutase(SOD)activity in lumbar spinal cord tissues were determined using chemical colorimetry.The neuron number and deviation rate in spinal cord anterior horn were observed histopathologically.Results There was no significant difference between L Gln group and I/R group in behavior scoring,SOD activity,content of MDA and Glu,neuron number and deviation rate of spinal cord(P>0.05);however,there was a significant difference in GSH content of spinal cord(P<0.05).M Gln group and I/R group differed significantly(P<0.05)in behavior scoring,SOD activity,content of MDA,Glu,GSH,neuron number and deviation rate of spinal cord.Between H Gln group and M Gln group,there was no significant difference in behavior scoring,content of MDA and Glu,SOD activity,neuron number and aberration rate in spinal cord(P>0.05),whereas there was a significant difference in SOD activity and Glu content(P<0.05).Conclusion Pretreatment with medium-dose glutamine has a protective effect on spinal cord ischemia-reperfusion injury in rabbits,which may be related to the maintenance of GSH content,increase of SOD activity and reduction of MDA.

Inhibition of glutathione on vascular smooth muscle cell proliferation mediate by advanced glycation end products

Background To confirm the proliferation of vascular smooth muscle cell （VSMC） lead by advanced glycation end products （AGEs） and investigate weather the mechanism is work through MAPK pathway. To investigate weather the prolification of VSMC lead by AGEs can be inhibited by reduced glutathione（GSH） and what the mechanisam is. Methods VSMC of rats were isolated and cultivated, separated in 8 groups, each group contained 12 samples. Density of cell was 1×105 /mL in each sample, cultivated with AGEs at different concentrations and intervened with GSH at different concentrations. In order to determine the mechanism and interventional factors of VSMCs, sandwich ELISA method was used to test the concentration of P-P38 and MTT colorimetry was adopted to evaluate the amount of VSMC. Results 1.Effect of AGEs to the OD value of MTT in VSMC： with stimulation of AGEs, OD valued of P-P38 in VSMC increased simultaneously （P0.01）, their value were 0.43±0.15, 0.49±0.16, 0.48±0.19 [L/（g·cm）]. With the increase of the dose of AGEs, there were no difference between groups B, C of MTT OD value（P0.05）. 2.Effect of GSH to the OD value of MTT in VSMC stimulated by AGEs： OD value of MTT decreased with the increase of GSH concentration, their value were 0.347±0.102, 0.333±0.108, 0.285±0.080 [L/（g·cm）] respectively, decreased by 45%, 56%, 60%（P0.01）compared with value of AGEs control group. With the increasing of the dose of GSH, the MTT OD value had no difference between groups F, G and H （P0.05）. 3.Effect of AGEs to the OD value of P-P38 in VSMC： with stimulation of AGEs, OD valued of P-P38 in VSMC increased obviously （P0.01）, their value were 0.65±0.17, 0.85±0.26, 0.94±0.17 [L/（g·cm）]. With the increasing of the dose of AGEs, the P-P38 OD value increase simultaneously（P0.05）. 4.Effect of GSH on the OD value of P-P38 in VSMC stimulated by AGEs： OD value of P-P38 decreased with the increasing of GSH concentration, their value were 0.356±0.090, 0.281±0.070, 0.256±0.072 [L/（g·cm）] respectively, decreased by 45%, 56%, 60%（P0.01）compared with the value of control group. With the increasing of the dose of GSH, the P-P38 OD value between groups F, G and H were decreased gradually （P0.01）. Conclusions 1.AGEs has the function of inducing the proliferation of vascular SMC, the activation of the P-P38 MAPK signal pathway may be the mechanism of the proliferation of VSMC. 2.GSH can inhibit the proliferation of VSMC lead by AGEs, The P-P38-MAPK pathway is being blocked by GSH, which is the mechanism of inhibiting the proliferation of VSMC lead by AGEs.

Determination of the mechanism of photoinduced toxicity of selected metal oxide nanoparticles(ZnO,CuO,Co_3O_4 and TiO_2)to E.coli bacteria

Cytotoxicity of selected metal oxide nanoparticles（MNPs）（ZnO,CuO,Co 3 O 4 and TiO 2）was investigated in Escherichia coli both under light and dark conditions.Cytotoxicity experiments were conducted with spread plate counting and the LC 50 values were calculated.We determined the mechanism of toxicity via measurements of oxidative stress,reduced glutathione,lipid peroxidation,and metal ions.The overall ranking of the LC 50 values was in the order of ZnO 〈 CuO 〈 Co 3 O 4 〈 TiO 2 under dark condition and ZnO 〈 CuO 〈 TiO 2 〈 Co 3 O 4 under light condition.ZnO MNPs were the most toxic among the tested nanoparticles.Our results indicate depletion of reduced glutathione level and elevation of malondialdehyde level correlated with the increase in oxidative stress.Released metal ions were found to have partial effect on the toxicity of MNPs to E.coli.In summary,the dynamic interactions of multiple mechanisms lead to the toxicity of the tested MNPs to E.coli.

Enzyme-electrolytic degradation of dichloromethane: Efficiency, kinetics and mechanism

Enzymatic electrolysis cell(EEC)has advantages over microbial electrolysis cell(MEC)due to the needless of microbe inoculation and high-efficiency of enzymatic reaction.In this study,an EEC was first applied to achieve the effective degradation of halogenated organic pollutants and dichloromethane(CH2Cl2)was utilized as a model pollutant.The results indicate that the degradation efficiency of CH2Cl2 after 2 hr reaction in the EEC was almost100%,which was significantly higher than that with enzyme(51.1%)or current(19.0%).The current induced the continuous regeneration of reduced glutathione(GSH),thus CH2Cl2 was degraded under the catalysis of GSH-dependent dehalogenase through stepwise dechlorination,and successively formed monochloromethane(CH3Cl)and methane(CH4).The kinetic result shows that with a current of 15 mA,the maximum specific degradation rate of CH2Cl2(3.77×10-3 hr-1)was increased by 5.7 times.The optimum condition for CH2Cl2 dechlorination was also obtained with pH,current and temperature of 7.0,15 mA and 35°C,respectively.Importantly,this study helps to understand the behavior of enzymes and the fate of halogenated organic pollutants with EEC,providing a possible treatment technology for halogenated organic pollutants.

Antioxidant and modulatory role of Chlorophytum borivilianum against arsenic induced testicular impairment

Arsenic has a suppressive influence on spermatogenesis and induces impairment in male reproductive system due to oxidative stress. The present study was aimed to test the arsenic induced toxicity and protection by Chlorophytum borivilianum. The effect of sodium arsenite （4 mg/（kg body weight （bw）.day）） via double distilled water without or with C. borivilianum （800 mg/（kg bw.day）） was evaluated in Swiss albino mice for 30 days. The radical scavenging activity of the aqueous C. borivilianum root extract was measured using DPPH （1,1-diphenyl-2-picryl hydrayzyl） radical. Qualitative assessment of various cell types in the testis, sperm count and motility, testicular activity of lipid peroxidation （LPO）, reduced glutathione （GSH）, acid and alkaline phosphatase, cholesterol and serum testosterone were monitored. Arsenic treatment showed a significant increase in LPO, acid and alkaline phosphatase, cholesterol and decrease in sperm count, sperm motility, GSH and serum testosterone. Combined treatment showed significant decrease in LPO, acid and alkaline phosphatase, cholesterol and elevation in sperm count, sperm motility, GSH and serum testosterone. Testicular histopathology showed that C. borivilianum had reduced degeneration of germ cell in the seminiferous tubules and loss of sperms induced by arsenic intoxication. The results thus led us to conclude that administration of C. borivilianum root extract is found to be protective against arsenic induced toxicity.

Neuroprotective role of antioxidant and pyranocarboxylic acid derivative against AlCl_(3) induced Alzheimer’s disease in rats

Objective:To assess potential of quercetin and etodolac to treat oxidative stress in neuronal death and inflammation in Alzheimer’s disease of AlCl3 induced rat models.All results of this AlCl_(3)model are compared with those obtained in controls.Methods:Wistar rats,housed in a controlled environment were treated with aluminum chloride(4.2 mg/kg of body weight,i.p.)for 28 d rather than oral to ensure neurotoxic concentration in hippocampus and hypothalamic region,part highly active in memory control and cognition,while control group was injected with saline.Estimation of thiobarbituric acid reactive substance,superoxide dismutase,reduced glutathione and acetylcholine levels gave estimation of neuronal damage.Low(20 mg/kg and 25 mg/kg)and high(40 mg/kg and 50 mg/kg)doses of quercetin and etodolac were administered to the test groups respectively.Histopathology study was conducted to perform relative study.Results:Co-administration of quercetin and etodolac either alone or in combination prevented the changes in biochemical markers of Alzheimer’s disease,but significant results(P<0.05)were seen when a combination of two was administered at low dose levels.Good correlation was developed between chemical estimations and histopathology study.Conclusions:Our findings suggest a combined role of anti-oxidant and cyclooxygenase inhibitor in protection of neural degeneration and inflammation due to oxidative stress.

Recent advances in enhancing reactive oxygen species based chemodynamic therapy

Chemodynamic therapy(CDT),defined as an in situ oxidative stress response catalyzed by the Fenton or Fenton-like reactions to generate cytotoxic hydroxyl radicals(•OH)at tumor sites,exhibits conspicuous inhibition of tumor growth.It has attracted extensive attention for its outstanding edge in effectiveness,lower systemic toxicity and side effects,sustainability,low cost and convenience.However,the inconfor-mity of harsh Fenton reaction conditions and tumor microenvironment hamper its further development,based on which,numerous researchers have made efforts in further improving the efficiency of CDT.In this review,we expounded antitumor capacity of CDT in mechanism,together with its limitation,and then summarized and came up with several strategies to enhance CDT involved tumor therapy strategies by 1)improving catalytic efficiency;2)increasing hydrogen peroxide levels at tumor sites;3)reducing glutathione levels at tumor sites;4)applying external energy intervention;5)amplifying the distribu-tion of hydroxyl radicals at tumor sites;and 6)combination therapy.Eventually,the perspectives and challenges of CDT are further discussed to encourage more in-depth studies and rational reflections.