Benzylideneacetophenone derivative (1E)-1-(4-hydroxy-3-methoxyphenyl) hept-1-en-3-one (JC3) elicited cytotoxic effects on MDA-MB 231 human breast cancer cells-radiation resistant cells (MDA-MB 231-RR), in a dose-dependent manner, with an IC₅₀ value of 6 μM JC3. JC3-mediated apoptosis was confirmed by increase in sub-G1 cell population. JC3 disrupted the mitochondrial membrane potential, and reduced expression of anti-apoptotic B cell lymphoma-2 protein, whereas it increased expression of pro-apoptotic Bcl-2-associated X protein, leading to the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In addition, JC3 activated mitogen-activated protein kinases, and specific inhibitors of these kinases abrogated the JC3-induced increase in apoptotic bodies. JC3 increased the level of intracellular reactive oxygen species and enhanced oxidative macromolecular damage via lipid peroxidation, protein carbonylation, and DNA strand breakage. Considering these findings, JC3 is an effective therapy against radiation-resistant human breast cancer cells.
Apoptosis* ; bcl-2-Associated X Protein ; Breast Neoplasms* ; Breast* ; Caspase 3 ; Caspase 9 ; Chalcone* ; DNA ; Extracellular Vesicles ; Humans* ; Lipid Peroxidation ; Membrane Potential, Mitochondrial ; Mitogen-Activated Protein Kinases ; Oxidative Stress* ; Phosphotransferases ; Protein Carbonylation ; Reactive Oxygen Species

OBJECTIVE: To explore the role of hydrogen sulfide (H2S) in acute liver injury induced by crushing hind limbs of rats. METHODS: The rats were randomly divided into the following groups: control, crushing, H2S donor sodium hydrosulfide (NaHS) + crushing, H2S inhibitor propargylglycine (PAG) + crushing group. The acute liver injury model was established by 'crushing the hind limbs of rats with standard weight. Rats were sacrificed at 30 min and 120 min after the crush. The activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured by colorimetric method, and the content of H2S in plasma and the contents of malondialdehyde (MDA), protein carbonyl, glutathione (GSH) in the liver and the activity of H2S generating enzyme (cystathionine y-lyase, CSE) were determined by chemical method. The expression of CSE mRNA in liver was detected by RT-PCR. RESULTS: For crush injury group, the levels of AST and ALT in serum, MDA and protein carbonyl in liver increased. The levels of GSH, CSE, CSE mRNA in liver and H2S in serum decreased. The administration of NaHS before limbs crush could attenuate the changes of liver injury, but the pre-treatment with PAG could exacerbate the changes. CONCLUSION The decrease of H2S production could involve in mediating the acute liver injury induced by traumatic stress in rats.
Alanine Transaminase/blood* ; Alkynes/pharmacology* ; Animals ; Aspartate Aminotransferases/blood* ; Cystathionine gamma-Lyase/metabolism* ; Glutathione/metabolism* ; Glycine/pharmacology* ; Hydrogen Sulfide/pharmacology* ; Liver/injuries* ; Malondialdehyde/metabolism* ; Protein Carbonylation ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sulfides/pharmacology*

Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group (P<0.01), while obviously reduced the MDA and PCO contents and the ROS levels derived from of the brain mitochondria. The shikonin also noticeably improved the spatial memory deficits caused by carbon ion beam irradiation. All results demonstrated that shikonin could improve the irradiated brain injury which might resulted from its modulation effects on the oxidative stress induced by the 12C6+ ion beam.
Animals ; Antioxidants ; pharmacology ; Brain Injuries ; prevention & control ; Catalase ; metabolism ; Heavy Ion Radiotherapy ; Male ; Malondialdehyde ; metabolism ; Mice ; Naphthoquinones ; pharmacology ; Protein Carbonylation ; Radiation Injuries, Experimental ; prevention & control ; Radiation-Protective Agents ; pharmacology ; Random Allocation ; Specific Pathogen-Free Organisms ; Superoxide Dismutase ; metabolism

OBJECTIVE: To explore the prevalence, clinical feature and levels of protein carbonyl (PCO) in serum of type 2 diabetes mellitus combining obstrucitive sleep apnea syndrome (OSAHS). METHOD: Two hundred and three patients with type 2 diabetes were taken multi lead sleep detection and their AHI, age, height, body mass index (BMI),waistline, duration of diabetes, fast blood glucose, HbA1c level and level of PCO in serum were recorded. RESULT: The prevalence of OSAHS was 79.2% in 203 patients, serious apnea 30.4%, moderate apnea 45.4%, mild apnea 24.2%. BMI, waistline, fast blood glucose, HbA1c level and level of PCO in serum were higher in patients complicated with OSAHS (P < 0.01). HbA1c was independently and positively correlated with patients with OSAHS risk (P < 0.05, OR 6.11). The independent correlation factors of AHI included HbA1c level,BMI, waistline, duration of diabetes and level of PCO in serum,with HbA1c as the predominant factor (P < 0.05). CONCLUSION The prevalence of OSAHS was higher in patients of type 2 diabetes mellitus combining (OSAHS). Moreover, in these patients poor glucose control and aggravated protein oxidative injury were observed.
Body Mass Index ; Diabetes Mellitus, Type 2 ; blood ; complications ; Humans ; Prevalence ; Protein Carbonylation ; Risk Factors ; Sleep Apnea, Obstructive ; blood ; complications

OBJECTIVETo study the effect of Anthocyanin (Ay) on Cadmium-Induced Mouse testis Damage.

METHODSMouse testis damage model were constructed and testis malonaldehyde (MDA) and protein carbonxyl content (PCO), as well as catalase (CAT) and superoxide dismutase (SOD) were determined.

RESULTSThe intoxication of cadmium can cause the increase of MDA and PCO content in mouse testis (P < 0.05), however, the activities of SOD and CAT were altered (P < 0.01).

CONCLUSIONAy have the strong potent to scavenge free radicals, owing to its special chemical structures, and act as a protector to inhibit the oxidative stress induced by cadmium.

Animals ; Anthocyanins ; chemistry ; pharmacology ; Cadmium ; toxicity ; Catalase ; drug effects ; Male ; Malondialdehyde ; analysis ; Mice ; Oxidative Stress ; Protein Carbonylation ; drug effects ; Superoxide Dismutase ; drug effects ; Testis ; drug effects

OBJECTIVETo investigate the role of oxidative stress in the endoplasmic reticulum stress-induced apoptosis of alveolar macrophages triggered by quartz dust.

METHODSSeventy-two healthy adult Wistar rats were randomly divided into control group, quartz dust group, quartz dust plus N-acetyl cysteine (NAC) group, and NAC group, with 18 rats in each group. One milliliter of sterile saline (for the control and NAC groups) or 1 ml of saline with 5%ultrafine quartz dust (for dust group and dust plus NAC group) was given to each rat by non-exposed endotracheal infusion. From the second day after dust infusion, rats in dust plus NAC group and NAC group received intragastric administration of NAC (100 mg/kg). In each week, the treatment with NAC lasted for 5 consecutive days, followed by 2 days' interval. For each group, 6 rats were randomly selected on the 14th, 28th, or 56th day after dust exposure; they were sacrificed by bloodletting from the femoral artery, and the lungs were collected. Bronchoalveolar lavage fluid was collected to separate macrophages. The protein expression of caspase-12 in alveolar macrophages, the apoptosis rate and reactive oxygen species (ROS) content of alveolar macrophages, and the protein carbonyl content of alveolar macrophages were determined by Western blot, flow cytometry, and colorimetry, respectively.

RESULTSIncreased protein expression of caspase-12, apoptosis rate, and content of ROS and protein carbonyl were discovered on the 14th day in the dust group, in comparison with the control group (P < 0.05), and the increase lasted till the 28th and 56th days. (P < 0.05). Compared with the dust group, the dust plus NAC group showed significant decreases in the content of ROS on the 14th, 28th, and 56th days (P < 0.05), significant decreases in the content of protein carbonyl on the 28th and 56th days (P < 0.05), and significant decreases in the protein expression of caspase-12 and apoptosis rate (P < 0.05).

CONCLUSIONOxidative stress is potentially involved in the endoplasmic reticulum stress-induced apoptosis of alveolar macrophages triggered by quartz dust. Oxidative damage of protein in the endoplasmic reticulum may play an important role in the process.

Animals ; Caspase 12 ; metabolism ; Dust ; Endoplasmic Reticulum Stress ; drug effects ; Macrophages, Alveolar ; drug effects ; pathology ; Male ; Oxidative Stress ; drug effects ; Protein Carbonylation ; Quartz ; toxicity ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism

Ionizing radiation can induce cellular oxidative stress through the generation of reactive oxygen species, resulting in cell damage and cell death. The aim of this study was to determine whether the antioxidant effects of the flavonoid fisetin (3,7,3',4'-tetrahydroxyflavone) included the radioprotection of cells exposed to gamma-irradiation. Fisetin reduced the levels of intracellular reactive oxygen species generated by gamma-irradiation and thereby protected cells against gamma-irradiation-induced membrane lipid peroxidation, DNA damage, and protein carbonylation. In addition, fisetin maintained the viability of irradiated cells by partially inhibiting gamma-irradiation-induced apoptosis and restoring mitochondrial membrane potential. These effects suggest that the cellular protective effects of fisetin against gamma-irradiation are mainly due to its inhibition of reactive oxygen species generation.
Antioxidants ; Apoptosis ; Cell Death ; DNA Damage ; Lipid Peroxidation ; Membrane Potential, Mitochondrial ; Membranes ; Oxidative Stress* ; Protein Carbonylation ; Radiation, Ionizing ; Reactive Oxygen Species

Fibrinogen is a key protein involved in coagulation and its deposition on blood vessel walls plays an important role in the pathology of atherosclerosis. Although the causes of fibrinogen (fibrin) deposition have been studied in depth, little is known about the relationship between fibrinogen deposition and reactive carbonyl compounds (RCCs), compounds which are produced and released into the blood and react with plasma protein especially under conditions of oxidative stress and inflammation. Here, we investigated the effect of glycolaldehyde on the activity and deposition of fibrinogen compared with the common RCCs acrolein, methylglyoxal, glyoxal and malondialdehyde. At the same concentration (1 mmol/L), glycolaldehyde and acrolein had a stronger suppressive effect on fibrinogen activation than the other three RCCs. Fibrinogen aggregated when it was respectively incubated with glycolaldehyde and the other RCCs, as demonstrated by SDS-PAGE, electron microscopy and intrinsic fluorescence intensity measurements. Staining with Congo Red showed that glycolaldehyde- and acrolein-fibrinogen distinctly formed amyloid-like aggregations. Furthermore, the five RCCs, particularly glycolaldehyde and acrolein, delayed human plasma coagulation. Only glycolaldehyde showed a markedly suppressive effect on fibrinogenesis, none did the other four RCCs when their physiological blood concentrations were employyed, respectively. Taken together, it is glycolaldehyde that suppresses fibrinogenesis and induces protein aggregation most effectively, suggesting a putative pathological process for fibrinogen (fibrin) deposition in the blood.
Acetaldehyde ; analogs & derivatives ; blood ; chemistry ; Acrolein ; blood ; chemistry ; Blood Coagulation ; Congo Red ; Electrophoresis, Polyacrylamide Gel ; Fibrinogen ; chemistry ; metabolism ; Glyoxal ; blood ; chemistry ; Humans ; Malondialdehyde ; chemistry ; Polymerization ; Protein Carbonylation ; Pyruvaldehyde ; blood ; chemistry ; Solutions ; Spectrometry, Fluorescence ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Thrombin ; chemistry

BACKGROUND: Although reactive oxygen species (ROS) have been produced in both mouse bone marrow-derived dendritic cells (DCs) and XS-106 DCs by contact sensitizers and irritants in previous studies, the generation of ROS in human monocyte-derived DCs (MoDCs) and their role in contact hypersensitivity (CHS) has yet to be elucidated. OBJECTIVE: The purpose of this study was to determine whether contact allergens and irritants induce ROS in MoDCs and, if so, to evaluate the role of contact allergen and irritant induced-ROS in MoDCs in CHS. METHODS: Production of ROS was measured by 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA) assay. Surface CD86 and HLA-DR molecules were detected by flow cytometry. Protein carbonylation was detected by Western blotting. RESULTS: ROS were produced by contact allergens such as dinitrochlorobenzene (DNCB) and thimerosal and the irritant benzalkonium chloride (BKC). DNCB-induced, but not BKC-induced, ROS increased surface CD86 and HLA-DR molecules on MoDCs and induced protein carbonylation. These changes were reduced in the presence of antioxidant N-acetyl cysteine. CONCLUSION: Our results suggest that DNCB-induced ROS may be different from those induced by irritant BKC. The DNCB-induced ROS may be associated with the CHS response, because they activate surface molecules on DCs that are important for generating immune reactions.
Allergens ; Animals ; Benzalkonium Compounds ; Blotting, Western ; Cysteine ; Dendritic Cells ; Dermatitis, Contact ; Dinitrochlorobenzene ; Flow Cytometry ; HLA-DR Antigens ; Humans ; Irritants ; Mice ; Protein Carbonylation ; Reactive Oxygen Species ; Thimerosal

OBJECTIVE: To investigate the lipid peroxide levels and protein carbonyls levels in the amniotic fluid of pregnant women with preterm premature rupture of membranes (PPROM). METHODS: The lipid peroxide levels in the amniotic fluid of normal pregnancy (n=20) and pregnant women with PPROM (n=20) were measured by thiobarbituric acid reaction. The protein carbonyl contents in the amniotic fluid of normal pregnancy (n=20) and pregnant women with PPROM (n=20) were determined by the 2,4-dinitrophenylhydrazine method. After amniotic fluid of them were mixed and incubated up to 5 hours with 0.2 mL of 1mM moxalactam, cefodizime, amoxacillin, erythromycin, the lipid peroxide levels and protein carbonyl contents in them were measured. RESULTS: 1. The lipid peroxide levels in the amniotic fluid of pregnant women with PPROM was significantly higher than that of normal pregnancy (9.74+/-0.48 vs. 7.20+/-0.38 nmol/mg protein, P<0.01). 2. The protein carbonyl levels in the amniotic fluid of pregnant women with PPROM was significantly higher than that of normal pregnancy (13.0+/-0.33 vs. 11.27+/-0.17 nmol/mg protein P<0.01). 3. The lipid peroxide levels and protein carbonyls formation by moxalactam in the amniotic fluid of pregnant women with PPROM was significantly higher than basal level (12.08+/-0.81 vs. 9.74+/-0.48 nmol/mg protein, 20.08+/-0.66 vs. 13.0+/-0.33 nmol/mg protein, P<0.01). 4. The lipid peroxide levels and protein carbonyls formation by cefodizime in the amniotic fluid of pregnant women with PPROM was significantly lower than basal level (5.04+/-0.33 vs. 9.74+/-0.48 nmol/mg protein, 9.76+/-0.35 vs. 13.0+/-0.33 nmol/mg protein, P<0.01). 5. There were no significant differences in the levels of lipid peroxide and protein carbonyls by amoxacillin and erythromycin in the amniotic fluid of pregnant women with PPROM between antibiotics-induced and basal levels. CONCLUSION: The lipid peroxidation and the protein carbonyls formation were increased in the amniotic fluid of pregnant women with PPROM. Antibiotics-induced lipid peroxide and protein carbonyl levels were changed in the amniotic fluid of pregnant women with PPROM. Further studies on our results may be beneficial in the selection of antibiotics for pregnant women with PPROM.
Amniotic Fluid ; Anti-Bacterial Agents ; Cefotaxime ; Erythromycin ; Female ; Humans ; Lipid Peroxidation ; Membranes ; Moxalactam ; Phenylhydrazines ; Pregnancy ; Pregnant Women ; Protein Carbonylation ; Rupture ; Thiobarbiturates