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OBJECTIVE: To design and synthesize phenylpyridine substituted semicarbazides and investigate their in vitro antitumor activities. METHODS: The target compounds were synthesized from acetophenone through condensation, cyclization,hydrazinolysis and reaction with isocyanates. The synthesized compounds were screened for their anticancer potential against different cancer cells viz human hepatocelular carcinoma (QGY-7703), non-small cell lung (NCl-H460) and human breast (MCF-7) cancer cell lines by MTT assay. RESULTS Sixteen novel compounds were obtained, and their structures were characterized by 1H-NMR, 13C-NMR and HRMS. In vitro bioassay indicated that most compounds had a certain degree of antitumor activity. Compound 51 displayed the most potential anticancer activity against these cancer cell lines with IC50 value of 9.15, 10.45 and 12.50 μmol·L-1, respectively. CONCLUSION: The series of compounds show preferable antitumor activities, which are worthy of further study.
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A sensitive electrochemical sensor for the detection of semicarbazide ( SEM ) based on the glassy carbon electrode modified with carboxylated multi-walled carbon nanotube ( CMWCNTs ) was constructed in this work. The modified materials were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy and electrochemical impedance spectroscopy. The results showed that the CMWCNTs exhibited a certain degree of changes, such as the appearance of the characteristic peaks of carbon oxygen double bonds in carboxyl group, a decrease in diameter and length and a remarkable reduction of the impedance value. The electrochemical behavior of SEM on CMWCNTs/GCE was investigated by cyclic voltammetry and amperometric i-t curve in 1 mol/L HAc-NaAc buffer solution. An irreversible oxidation peak of SEM appeared at CMWCNTs/GCE. Compared to the bare electrode, the current of the oxidation peak was significantly increased. Under the optimal conditions such as HAc-NaAc solution ( pH 7 ) and scan rate of 0. 1 V/s, the obtained sensor presented linear response to SEM concentration in the range of 5. 0 × 10-6 mol/L-1. 09×10-3 mol/L, the linear regression equation was Ip(μA)=-0. 472+0. 0599C (μmol/L) with linear correlation coefficient of 0. 997. The detection limit was 1. 88×10-7 mol/L. At the same time, the recovery was from 92. 8% to 98. 0% in the test of pork liver samples.
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A sensitive electrochemical sensor for the detection of semicarbazide ( SEM ) based on the glassy carbon electrode modified with carboxylated multi-walled carbon nanotube ( CMWCNTs ) was constructed in this work. The modified materials were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy and electrochemical impedance spectroscopy. The results showed that the CMWCNTs exhibited a certain degree of changes, such as the appearance of the characteristic peaks of carbon oxygen double bonds in carboxyl group, a decrease in diameter and length and a remarkable reduction of the impedance value. The electrochemical behavior of SEM on CMWCNTs/GCE was investigated by cyclic voltammetry and amperometric i-t curve in 1 mol/L HAc-NaAc buffer solution. An irreversible oxidation peak of SEM appeared at CMWCNTs/GCE. Compared to the bare electrode, the current of the oxidation peak was significantly increased. Under the optimal conditions such as HAc-NaAc solution ( pH 7 ) and scan rate of 0. 1 V/s, the obtained sensor presented linear response to SEM concentration in the range of 5. 0 × 10-6 mol/L-1. 09×10-3 mol/L, the linear regression equation was Ip(μA)=-0. 472+0. 0599C (μmol/L) with linear correlation coefficient of 0. 997. The detection limit was 1. 88×10-7 mol/L. At the same time, the recovery was from 92. 8% to 98. 0% in the test of pork liver samples.
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A method for rapid determination of semicarbazide in water by hydrophilic interaction chromatography-quadrupole / electrostatic field orbitrap high resolution mass spectrometry was developed. The sample was extracted with acetonitrile after 0. 1 mol/ L NaOH was added in the sample and then excessive amounts of Na2 SO4 was added to stratify acetonitrile from the mix solution. The acetonitrile extraction solution was dehydrated with anhydrous sodium sulfate. The preparation was separated by an amide column using as hydrophilic interaction column, and gradient elution program was employed by using water and acetonitrile containing 0. 1% formic acid as mobile phase, then it was detected in positive and selected ion monitoring mode by a quadrupole / electrostatic field orbitrap high resolution mass spectrometry. Internal standard method was used for quantitative analysis. The linear correlation coefficient of semicarbazide was 0. 997 in the concentration range of 0. 2 -20 μg / L under the optimal conditions. The limit of detection was 0. 09 μg / L, while the limit of quantitation was 0. 30 μg / L. The recoveries were 82. 3% to 92. 0% , and the relatively standard deviations were less than 7. 6% at the spiked levels of 0. 5, 1. 0 and 5. 0 μg / L using river water and sea water as blank samples. The developed method is suitable for the analysis of trace semicarbazide in environment water samples.
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[ ABSTRACT] AIM:To observe the effect of the metabolites generated from oxidative deamination of methylamine ( MA) or benzylamine ( BZA ) catalyzed by semicarbazide-sensitive amine oxidase ( SSAO ) on 3T3-L1 adipocytes. METHODS:3T3-L1 preadipocytes were induced to differentiation.SSAO activity was determined by high performance liquid chromatography ( HPLC) at different differentiation time points.MTT assay was applied to detect cell vitality after exposure to different concentrations of MA or BZA.Fluorescence probe DCFH-DA was used to determine the production of reactive oxygen species after incubation of 3T3-L1 adipocytes with MA or BZA.After exposure to 0.5 mmol/L MA or BZA for 4 h, malondialdehyde ( MDA) , total superoxide dismutase ( T-SOD) and glutathione ( GSH) in the adipocytes or prea-dipocytes were measured.RESULTS:SSAO activity increased with the increase in the differentiation days, and reached a maximum at the 8th day.Incubation of the cells with different concentrations of MA or BZA for 4 h did not significantly de-creased the cell vitality (P>0.05).After exposure to 0.5 mmol/L MA or BZA, the reactive oxygen species in adipocytes significantly increased, and were about 3 to 4 times as compared with control group (P0.05 ) .CONCLUSION: MA or BZA induces oxidative stress in the mature adipocytes, which might result from the deamination products catalyzed by SSAO.
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Objective To observe the expression and activity changes of vascular adhesion protein-1 (VAP-1) in the small intestine and serum of rats during severe hemorrhagic shock and resuscitation, and to study its influence on shock prognosis. Methods Fifty rats were evenly randomized into sham group, hemorrhagic shock group, shock resuscitation group, control recovery group and the experimental recovery group. Rat models of severe hemorrhagic shock and resuscitation were established. Before shock, 1 hour after shock and 1 hour after resuscitation, the expressions of VAP-1 protein and mRNA in the intestinal tissues of rats were examined by Western blotting analysis and real-time RT-PCR, respectively; and the serum levels of VAP-1 and its activities were determined by ELISA kit. Rats in the experimental recovery group was resuscitated by injection of 20 mg/kg 2-bromoethylamine and those in the control recovery group were given 1 mL/kg normal saline, and then the blood pressure, intestinal mucosa injury (Chiu’s score), small intestinal epithelial cell apoptosis (TUNEL detection) and 24-hour survival rates were compared between the two recovery groups. Results The intestinal VAP-1 protein and mRNA expressions and the serum VAP-1 and its activities in the severe hemorrhagic shock group were significantly higher than those in the sham shock group (P<0.05). Compared with the shock group, the above parameters were decreased in the recovery group, but were still higher than those in the sham group. Compared with the saline control group, 20 mg/kg 2-bromoethylamine significantly increased the blood pressure of animals 1 h and 24 h after recovery (P = 0.010, 0.039), significantly improved the Chiu’s score and apoptosis index of small intestinal epithelial cells (P = 0.022, P = 0.002), and improved the 24-hour survival rates of rats(90% to 60%). Conclusion The levels of VAP-1 and its activities are increased in severe hemorrhagic shock rats, and fluid resuscitation can inhibit this increase. Inhibition of VAP-1 activities can improve the low blood pressure, intestinal mucosa injury and apoptosis of small intestinal mucosa cells after the severe hemorrhagic shock and resuscitation, improving the 24-hour survival rates of rats.
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O objectivo do presente trabalho foi avaliar os efeitos da semicarbazida na morfologia testicular de ratos Wistar jovens. Os animais foram tratados durante 30 dias com hidrocloreto de semicarbazida incorporado na dieta, nas concentrações de 0, 3 e 6g/kg. Os resultados obtidos revelaram uma diminuição estatisticamente significativa no diâmetro dos túbulos seminíferos, no diâmetro do lúmen dos túbulos seminíferos e na área ocupada pelo epitélio seminífero nos animais dos grupos experimentais em comparação com os animais do grupo controlo. Estes resultados evidenciam que a semicarbazida induz alterações importantes no desenvolvimento testicular e sugerem um estudo mais aprofundado sobre os mecanismos de acção, dos efeitos a longo prazo, da reversibilidade das lesões e nas capacidades reprodutivas. Estes aspectos são relevantes numa perspectiva de segurança alimentar, em particular para as crianças, as quais representam um grupo de maior exposição e susceptibilidade à semicarbazida.
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The effects of semicarbazide hydrochloride on skeletal tissues were evaluated using Wistar rats. In the animals submitted to the administration of semicarbazide, radiological examination showed bone and articular alterations with growth plates enlargement. Histological exams showed irregular patterns and proliferation of chondrocytes and excessive accumulation of extracellular matrix. Immunohistochemical exams showed PCNA positive reaction in pre- and hypertrofic chondrocytes. These results confirm that semicarbazide induces important changes in skeletal tissues and that has potential utility in experimental osteolathryrism.
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The aim of this study was to determine the correlation between total nitrite/nitrate concentrations (NOx) and the kinetic parameters of monoamine oxidase enzymes (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) in human mesenteric arteries. Arteries were from non-diabetic and type 2 diabetic patients with sigmoid or rectum carcinoma for whom surgery was the first option and who were not exposed to neo-adjuvant therapy. Segments of human inferior mesenteric arteries from non-diabetic (61.1 ± 8.9 years old, 7 males and 5 females, N = 12) and type 2 diabetic patients (65.8 ± 6.2 years old, 8 males and 4 females, N = 12) were used to determine NOx concentrations and the kinetic parameters of MAO-A, MAO-B and SSAO by the Griess reaction and by radiochemical assay, respectively. The NOx concentrations in arteries from diabetic patients did not differ significantly from those of the non-diabetic group (10.28 ± 4.61 vs 10.71 ± 4.32 nmol/mg protein, respectively). In the non-diabetic group, there was a positive correlation between NOx concentrations and MAO-B parameters: Km (r = 0.612, P = 0.034) and Vmax (r = 0.593, P = 0.042), and a negative correlation with the SSAO parameters: Km (r = -0.625, P = 0.029) and Vmax (r = -0.754, P = 0.005). However, in the diabetic group no correlation was found between NOx concentrations and the three kinetic parameters of the enzymes. These results suggest an important function of sympathetic nerves and vascular NOx concentrations in arteries of non-diabetic patients. Thus, these results confirm the importance of a balance between oxidants and antioxidants in the maintenance of vascular homeostasis to prevent oxidative stress.
Subject(s)
Aged , Female , Humans , Middle Aged , Amine Oxidase (Copper-Containing)/metabolism , /metabolism , Mesenteric Arteries/chemistry , Monoamine Oxidase/metabolism , Nitrates/analysis , Nitrites/analysis , Case-Control Studies , /enzymology , Mesenteric Arteries/enzymology , Rectal Neoplasms/enzymology , Sigmoid Neoplasms/enzymologyABSTRACT
The fact that the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), together with superior colliculus, medial hypothalamus and amygdala, constitute the brain aversion system has been well-established. Stepwise increases in the intensity of electrical stimulation of dPAG or IC cause freezing and escape responses, which are followed by a freezing behavior that lasts after the interruption of the stimulation. Freezing and escape are unconditioned defensive behaviors derived from the stimulation of the output centers for the defense reaction, whereas the post-stimulation freezing is the behavioral counterpart of the processing of aversive information. Although GABA-A mechanisms of the midbrain tectum exert a tonic inhibitory influence on the neural substrates of unconditioned fear, their influence on the processing of aversive information is not completely understood. Thus, the present study examines the effects of injections of the GABA-A receptor agonist muscimol (1 and 2 nmol/0.2 µL) or the glutamic acid decarboxylase blocker semicarbazide (5 and 7.5 µg/0.2 µL) into dPAG or IC of Wistar rats on freezing and escape thresholds determined by electrical stimulation of these same structures and on post-stimulation freezing. Intra-dPAG injections of muscimol increased and semicarbazide decreased the freezing and escape thresholds of electrical stimulation of the dPAG. Only semicarbazide enhanced the dPAG post-stimulation freezing. Intra-IC injections of muscimol significantly increased aversive thresholds, while having no effect on IC post-stimulation freezing. Intra-IC injections of semicarbazide had no significant effects. These findings suggest that GABAergic mechanisms are important regulators of the expression of unconditioned fear in dPAG and IC, whereas only in dPAG GABA appears to play a role on the sensory gating towards aversive information during post-stimulation freezing.
Subject(s)
Animals , Aversive Therapy , Fear , GABA Agents , Inferior Colliculi , Periaqueductal GrayABSTRACT
AIM To study whether inhibition of semicarbazide (Sem)-sensitive amine oxidases (SSAO) attenuates myocardial ischemia-reperfusion (I-R) injury. METHODS Male Sprague-Dawley rats were randomly divided into 4 groups. Each group consisted of 10 rats. Sham group: the ligature was placed under the left coronary artery (LCA), but not ligated. Sham+Sem group: Sem (30 mg·kg-1, ip) was given 10 min prior to the experiment, the LCA ligature was not ligated. I-R group: the LCA was occluded for 30 min and reperfused for 180 min. I-R+Sem group: Sem (30 mg·kg-1, ip) was given 10 min prior to the experiment, and then 30 min ischemia followed by 180 min reperfusion. Myocardial infarct size was determined by using nitroblue tetrazolium staining. Plasma creatine kinase (CK) and myeloperoxidase (MPO) activities, and malondialdehyde (MDA) and hydroxyl radicals levels were determined by spectrophotometer. Plasma SSAO activity was determined by high performance liquid chromatography. HE staining was used for histopathological evaluation. RESULTS There were no significant differences on each index between sham and sham+Sem groups. Plasma MPO and SSAO activities, and MDA and hydroxyl radials levels significantly increased in I-R group, compared with sham group. Myocardial infarct size was remarkably smaller in I-R+Sem group (27.7±3.7)%, compared with I-R group (43.2±3.1)%. Plasma MDA level, MPO activity and hydroxyl radical level were lower in I-R+Sem group than those in I-R group, from (27.5±9.3) μmol·min-1·L-1,(2.6±0.4)mmol·L-1 and (628±50)mmol·min-1·L-1 down to (14.2±5.6)μmol·min-1·L-1,(1.7±0.5)mmol·L-1 and (503±88)mmol·min-1·L-1, respectively. Histological results showed that inhibition of SSAO activity significantly attenuated leukocyte infiltration. CONCLUSIONPlasma SSAO activity is increased in myocardial I-R injury and inhibition of SSAO can attenuate myocardial I-R injury.
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AIM To study whether chronic administration of methylamine may induce elevation of semicarbazide-sensitive amine oxidase (SSAO) activity and initiate the injury of cardiovascular endothelium. METHODS New Zealand rabbits were treated with methylamine hydrochloride (100 mg·kg-1) by ig, once a day for 6 months. The rabbits were weighed every other week and the dosage was adjusted according to the body weight. The number of circulating endothelial cells (CEC) in the arterial blood, nitric oxide (NO) concentration in the serum and ultrastructure of endothelial cells of aorta were assessed. The plasma SSAO activity and formaldehyde concentration were assessed by liquid chromatography. RESULTS The number of CEC, NO concentration, levels of SSAO activity and formaldehyde concentration in the methylamine group were increased significantly, compared with the control group. Ultrastructure of endothelial cells in the methylamine group showed inordinate morphological changes (multiple intranuclear inclusions, karyopyknosis and karyorrhexis). CONCLUSIONChronic administration of methylamine can induce the elevation of SSAO activity and initiate the injury of cardiovascular endothelium.