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1.
Life Sci ; 239: 117038, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730868

RESUMO

AIM: Disturbed placentation results in pregnancy complications like preeclampsia. Placental development is influenced by apoptosis during trophoblast differentiation and proliferation. Increased oxidative stress upregulates placental apoptosis. We have earlier reported increased oxidative stress, lower omega-3 fatty acids and vitamin E levels in women with preeclampsia. Current study examines effect of maternal omega-3 fatty acids and vitamin E supplementation on apoptotic markers across gestation in a rat model of preeclampsia. MAIN METHODS: Pregnant Wistar rats were randomly assigned to control; early onset preeclampsia (EOP); late onset preeclampsia (LOP); early onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (EOP + O + E) and late onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (LOP + O + E) groups. Animals (Control, EOP, EOP + O + E) were sacrificed at d14 and d20 of gestation while animals (LOP, LOP + O + E) were sacrificed at d20 to collect blood and placentae. Protein and mRNA levels of apoptotic markers were analyzed by ELISA and RT-PCR respectively. KEY FINDINGS: Protein levels of proapoptotic markers like Bcl-2 associated X-protein (BAX) (p < 0.05), caspase-8 and 3 (p < 0.01 for both) and malondialdehyde (p < 0.01) were higher only in the EOP group as compared to control. However, the antiapoptotic marker, B cell lymphoma 2 (Bcl-2) protein levels were lower in both the subtypes of preeclampsia (p < 0.01 for both). SIGNIFICANCE: Our findings suggest that supplementation was beneficial in reducing the caspase-8 and 3 in early onset preeclampsia but did not normalize BAX and Bcl-2 levels. This has implications for reducing placental apoptosis in preeclampsia.


Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Pré-Eclâmpsia/dietoterapia , Vitamina E/uso terapêutico , Animais , Apoptose/fisiologia , Biomarcadores/metabolismo , Caspase 3/análise , Caspase 3/sangue , Caspase 8/análise , Caspase 8/sangue , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/metabolismo , Feminino , Masculino , Fenômenos Fisiológicos da Nutrição/fisiologia , Estresse Oxidativo/fisiologia , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Vitamina E/metabolismo , Proteína X Associada a bcl-2/análise , Proteína X Associada a bcl-2/sangue
2.
Int J Rheum Dis ; 22(8): 1474-1478, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31211503

RESUMO

OBJECTIVE: Behçet's syndrome (BS) is a chronic, multisystemic and inflammatory syndrome. In our study, we aimed to compare the initiator, effector and inflammatory caspases and pannexin channel protein, which is thought to have an activity in inflammation, in the inflammatory process of BS, with healthy subjects, to investigate their level in patients and their relationship with the clinical findings. METHOD: Forty-six patients who were under follow-up for BS in the Sivas Cumhuriyet University Medical Faculty Department of Internal Diseases, Rheumatology Unit, between January 2017 and June 2017 and 44 healthy controls (HC) who did not have any rheumatic, systemic or metabolic diseases, were enrolled in this study. RESULTS: The mean serum pannexin-1 level was 6.36 (4.21-527.2) pg/mL in the BS group and 255.8 (5.38-2000) pg/mL in the HC group. Serum pannexin-1 levels were statistically significantly lower in the BS group (P < 0.0001). The measured mean serum caspase-3 level was 12.04 (11.25-43.69) pg/mL in the group with BS and 12.1 (11.19-484.3) pg/mL in the HC group (P = 0.143), mean serum caspase-9 level was 22 (5.14-29.33) pg/mL in the BS group and 22.01 (11.23-850) pg/mL in the HC group (P = 0.593), mean serum caspase-14 level was 6 (5.2-8.21) pg/mL in the BS group and 6.15 (5.7-353) pg/mL in the HC group (P = 0.053). CONCLUSION: Comparison of serum caspase-3, caspase-9 and caspase-14 levels in subjects with BS and in the HC group did not reveal any statistically significant differences. On the other hand, serum pannexin-1 levels were statistically significantly lower in the BS group.


Assuntos
Síndrome de Behçet/sangue , Conexinas/sangue , Proteínas do Tecido Nervoso/sangue , Adulto , Síndrome de Behçet/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Caspase 3/sangue , Caspase 9/sangue , Caspases/sangue , Regulação para Baixo , Feminino , Humanos , Masculino , Turquia
3.
Biomed Res Int ; 2019: 6539294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31240219

RESUMO

Chemotherapy leads to a loss of fertility and reproductive endocrine function, thereby increasing the risk of premature ovarian failure (POF). Studies have suggested that the transplantation of mesenchymal stem cells could inhibit apoptosis in ovarian granulosa cells and improve follicular development. In the present study, the effects of human umbilical cord mesenchymal stem cell (UCMSC) transplantation on ovarian function after ovarian damage caused by chemotherapy and the mechanism underlying these effects were investigated. POF model rats were obtained by the intraperitoneal injection of cyclophosphamide, and cultured UCMSCs were transplanted by tail vein injection. Serum estrogen, follicle-stimulating hormone, gonadotropin releasing hormone, and anti-Mullerian hormone levels were detected by ELISA. Folliculogenesis was evaluated by histopathological examination. The expression levels of nerve growth factor (NGF), high affinity nerve growth factor receptor (TrkA), follicle-stimulating hormone receptor (FSHR), and caspase-3 were evaluated by western blotting and RT-qPCR. The natural reproductive capacity was assessed by pregnant rate and numbers of embryos. The results indicated that UCMSC transplantation recovered disturbed hormone secretion and folliculogenesis in POF rats. NGF and TrkA levels increased, while FSHR and caspase-3 decreased. The pregnancy rate of POF rats was improved. Therefore, UCMSCs could reduce ovarian failure due to premature senescence caused by chemotherapy, and the NGF/TrkA signaling pathway was involved in the amelioration of POF.


Assuntos
Antineoplásicos/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Fator de Crescimento Neural/metabolismo , Insuficiência Ovariana Primária/terapia , Cordão Umbilical/transplante , Animais , Hormônio Antimülleriano/sangue , Apoptose/efeitos dos fármacos , Caspase 3/sangue , Ciclofosfamida/efeitos adversos , Estrogênios/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/sangue , Humanos , Células-Tronco Mesenquimais , Fator de Crescimento Neural/sangue , Ovário/patologia , Gravidez , Insuficiência Ovariana Primária/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Receptores do FSH/sangue
4.
Med Sci Monit ; 25: 1769-1779, 2019 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-30848248

RESUMO

BACKGROUND Cardiac remote ischemic conditioning (RIC) is a noninvasive cardioprotective method in ischemia-reperfusion injury and acute myocardial infarction (AMI). The aims of this study were to investigate the effects of RIC in a rat model of AMI. MATERIAL AND METHODS Adult male Sprague-Dawley rats included the AMI group that underwent ligation of the left anterior descending (LAD) coronary artery (n=24), the RIC group that consisted the AMI rat model treated with RIC once daily in the left hind limb until days 1, 7 and 14 (n=24), and the sham group (n=24). Myocardial infarct size was measured by routine histology with triphenyltetrazolium chloride (TTC) and Masson's trichrome histochemical staining for myocardial necrosis and fibrosis, respectively. Serum levels of Bcl-2, Bax, caspase-3, and inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptosis index was detected using the TUNEL assay. Spectrophotometry of the myocardium was used to identify mitochondrial complexes and myocardial ATP. RESULTS The RIC group showed improved cardiac hemodynamics, reduced the size of the myocardial infarction, upregulated expression of Bcl-2, and down-regulation of the levels of Bax, caspase-3, and iNOS, and reduced cardiac myocyte apoptosis and inhibited the opening of the mitochondrial permeability transition pore (MPTP). CONCLUSIONS In a rat model of AMI, RIC improved the hemodynamic index, reduce the levels of apoptosis and myocardial injury, and improved mitochondrial function.


Assuntos
Precondicionamento Isquêmico/métodos , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Cardiotônicos , Caspase 3/análise , Caspase 3/sangue , Modelos Animais de Doenças , Traumatismos Cardíacos/prevenção & controle , Hemodinâmica , Masculino , Mitocôndrias/metabolismo , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/terapia , Proteína X Associada a bcl-2/análise , Proteína X Associada a bcl-2/sangue
5.
Am J Cardiol ; 123(6): 899-904, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30617008

RESUMO

Evidence is accumulating that cardiac apoptosis occurs and contributes to myocyte cell death during myocardial ischemia. Cardioplegia, defined as the temporary cessation of cardiac activity during cardiac surgery, is a clinically controlled condition with myocardial ischemia and reperfusion. Our goal was to determine whether the apoptotic biomarker caspase-3 p17 is elevated in the coronary sinus (CS) during cardioplegia and if any elevations were reflected in the peripheral venous (PV) blood. Levels of the necrotic biomarker cardiac troponin I (cTnI) and the inflammatory marker caspase-1 p20 were also quantified in CS and PV. Blood was drawn before and at the end of cardioplegia in PV and CS and levels of p20, p17, and cTnI were measured. cTnI, p20, and p17 PV levels were significantly elevated compared with the control population before and at the end of cardioplegia. PV levels of all 3 markers increased after cardioplegia. CS levels were higher than PV levels for all 3 markers at both time points. Our data are consistent with the occurrence of cardiac apoptosis and inflammation during cardioplegia, in addition to necrosis. The heart-derived markers contributed to the peripheral levels and suggest that measurement of PV biomarker concentrations can be used to gauge cardiac preservation.


Assuntos
Caspase 1/sangue , Caspase 3/sangue , Parada Cardíaca Induzida/métodos , Isquemia Miocárdica/cirurgia , Revascularização Miocárdica/métodos , Idoso , Apoptose , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Masculino , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico , Miócitos Cardíacos/patologia , Prognóstico , Estudos Prospectivos , Troponina I/sangue
6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 34(10): 931-936, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30554587

RESUMO

Objective To investigate the clinical application value of circulating miR-29a in diagnosis and prognosis monitoring in acute pancreatitis (AP) patients, and to preliminary explore the molecular pathology significance of high expression of miR-29a. Methods 30 cases of mild acute pancreatitis (MAP) patients (MAP group) and 30 cases of moderately serve acute pancreatitis (MSAP) or serve acute pancreatitis (SAP) patients ( M-SAP group) were randomly selected, and 30 cases of healthy adults were used as control group. The general clinical data of each group were compared, and miR-29a levels in peripheral blood were measured by real tome quantitative PCR, then the correlation between miR-29a levels and Ranson score or APACHEIIscore were analyzed. The clinical usefulness of miR-29a for AP patients was assessed by ROC curve analysis. AR42J cells were treated with deoxycholic acid (DCA) to establish AP cell model, the expression levels of miR-29a and caspase-3 were detected. AR42J cells were transfected by lentiviral vector contain miR-29a mimic or miR-29a AMO and measured of expression levels of miR-29a and caspase-3. Results In acute phase, the expression of circulating miR-20a was up-regulated in MAP and M-SAP group patients, and miR-20a levels of M-SAP group patients were higher than MAP group patients. In same group, miR-20a levels in acute phase were higher than recovery phase. Correlation analysis indicated the positive correlation between miR-20a levels and Ranson score or APACHEII score. ROC curve analysis indicated that the AUC of miR-29a for diagnosis MAP patients was 0.961 ( 95%CI: 0.921~ 1.002), cut-off value was 1.460. The AUC of miR-29a for diagnosis M-SAP patients was 0.972 ( 95%CI: 0.939 ~ 1.004), cut-off value was 1.340. The expression levels of miR-29a and caspase 3 were increased in AP cell model. Moreover, caspase 3 levels in AP cell model were increased than vector control after overexpression of miR-29a, and caspase-3 levels were reduced than vector control after suppressing of miR-29a expression. Conclusion Circulating miR-29a is high expression in MAP and M-SAP patients, and high expression of miR-29a may relate to pancreatic acinar cell apoptosis, and this biomarkers has high clinical value in AP diagnosis and prognosis monitoring.


Assuntos
MicroRNAs/sangue , Pancreatite/sangue , Doença Aguda , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Caspase 3/sangue , Humanos , Pancreatite/diagnóstico , Prognóstico , Índice de Gravidade de Doença , Regulação para Cima
7.
Acta Cir Bras ; 33(10): 896-903, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30484499

RESUMO

PURPOSE: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). METHODS: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. RESULTS: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). CONCLUSION: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.


Assuntos
Lesão Pulmonar Aguda/fisiopatologia , Apoptose/fisiologia , Traumatismos por Explosões/fisiopatologia , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/patologia , Animais , Traumatismos por Explosões/sangue , Traumatismos por Explosões/patologia , Caspase 3/sangue , Modelos Animais de Doenças , Feminino , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Alvéolos Pulmonares/patologia , Coelhos , Distribuição Aleatória , Proteína X Associada a bcl-2/sangue
8.
Acta cir. bras ; 33(10): 896-903, Oct. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-973463

RESUMO

Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.


Assuntos
Animais , Masculino , Feminino , Coelhos , Traumatismos por Explosões/fisiopatologia , Apoptose/fisiologia , Lesão Pulmonar Aguda/fisiopatologia , Alvéolos Pulmonares/patologia , Traumatismos por Explosões/patologia , Traumatismos por Explosões/sangue , Distribuição Aleatória , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Modelos Animais de Doenças , Proteína X Associada a bcl-2/sangue , Caspase 3/sangue , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/sangue
9.
Gen Comp Endocrinol ; 268: 80-87, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30077795

RESUMO

Yaks (Bos grunniens) have special physiological structures that help them adapt to high-altitude environments. Survivin is actively studied in cancer tissues, but less in normal tissues. Therefore, the aim of the present study was to analysis the relationship between survivin expression and apoptosis rate in yaks. A partial gene sequence of survivin was cloned and characterized using bioinformatics. The expression of survivin was investigated using real-time quantitative PCR (RT-qPCR) and western blot (WB) analysis and localized using immunohistochemistry (IHC). The results revealed that in normal physiological organs, survivin is mainly expressed in cytoplasm and its expression was up-regulated with age. Its expression in heart and liver was higher than in other organs, such as spleen, lung, brain, kidney, and testis. It is noteworthy that the expression of survivin in spleen is differed from that in other organs. Therefore, we selected immune organs (lymph node, thymus and spleen) to investigate the relationship between survivin expression and apoptosis. Caspase-3 was used as a reference. Within the same age group, the expression of survivin was the highest in the spleen, but that of caspase-3 was the highest in the lymph node (P < 0.01). Furthermore, the IHC analysis revealed that survivin and caspase-3 are expressed in the same location (mainly in the cytoplasm, Hassall's corpuscles, the medulla of the lymph node, the red pulp and marginal zone of the spleen. More importantly, survivin expression was down-regulated with age in immune organs, and the opposite trend was observed for caspase-3 expression (P < 0.01). The results proved that the expression of survivin and caspase-3 is down- and up-regulated with age, respectively, suggesting that survivin and caspase-3 might coordinating and participating in slowing down the rate of apoptosis rate in immune organs of healthy yak.


Assuntos
Caspase 3/sangue , Animais , Bovinos , Humanos
10.
Bratisl Lek Listy ; 119(8): 469-475, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30160153

RESUMO

BACKGROUND: One of the important risk factors for dementia is chronic cerebral hypoperfusion (CCH) especially in patients with cerebrovascular disease. OBJECTIVES: In the present study, using rat model of bilateral common carotid artery occlusion, the possible protective effects of ethyl pyruvate (EP) have been explored in terms of memory impairment, oxidative stress, and levels of caspase-3, Na-K ATPase, and IL- 1ß. METHODS: Rats were treated with EP (50 mg/kg, i.p) for 4 weeks. Cognitive function was evaluated by Morris Water Maze (MWM). Both levels of caspase-3 and Na-K ATPase in tissue, IL-1ß in plasma were measured by ELISA method. Status of oxidative stress in brain was assessed by the measurements of the tissue malondialdehyde (MDA) and reduced glutathione (GSH) contents.  RESULTS: Results showed that CCH caused a striking impairment of spatial working memory, accompanied with increased levels of MDA and IL-1ß as well as caspase 3 level. The treatment with EP, however, significantly improved the memory impairment. Moreover, the treatment also provided beneficial effects on the disturbances of caspase 3, IL-1ß and MDA. CONCLUSION: This study strongly imply that the EP administration can alleviate the memory impairment observed due to CCH. The protection provided by EP may result from inhibition of inflammatory response, apoptotic processes and oxidative stress (Fig. 3, Ref. 58).


Assuntos
Isquemia Encefálica/tratamento farmacológico , Circulação Cerebrovascular/fisiologia , Transtornos Cognitivos/etiologia , Hipocampo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Piruvatos/química , Animais , Encéfalo/metabolismo , Isquemia Encefálica/patologia , Caspase 3/sangue , Caspase 3/efeitos dos fármacos , Cognição/fisiologia , Glutationa/metabolismo , Hipocampo/metabolismo , Interleucina-1beta/sangue , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Estresse Oxidativo/fisiologia , Piruvatos/uso terapêutico , Ratos , Memória Espacial
11.
J Stroke Cerebrovasc Dis ; 27(11): 3020-3029, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30150066

RESUMO

The manganese-dependent superoxide dismutase (MnSOD) Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of vascular diseases. Brain-Derived Neurotrophic Factor (BDNF) plays an essential role in the plasticity and neuronal regeneration of the brain after vascular injuries. However, little is known about interaction between MnSOD Ala16Val SNP on stroke, a frequent neurologic disease that involves various interacting pathways, such as vascular dysfunctions, inflammation, and neurotrophic factors. In this sense, the objective of this study was to investigate the relationship between MnSOD Ala16Val SNP with BDNF levels on stroke and also its influence on nitrosative stress, inflammatory, apoptotic, and DNA damage parameters. For this, 88 subjects were investigated, 44 subjects poststroke and 44 healthy controls. Questionnaires were applied to clinical characteristics and after laboratorial exams were collected. We analyzed levels of oxidative/nitrosative stress, inflammatory, apoptotic, and DNA damage markers. We showed a higher proportion of VV genotype in poststroke as compared to healthy subjects. Nitrite/nitrate, Tumor Necrosis Factor-α, Caspase 3 (CASP 3) and 8 (CASP 8) activation, Acethylcholinesterase (AChE), and Picogreen levels were higher in VV poststroke group, as well as BDNF and ACh levels were lower in VV and AV poststroke. We may suggest that V allele carries a worse outcome profile after stroke, relating to nitrosative stress, inflammatory, and apoptotic response. These events associated to a BDNF reduction, probably, contribute to the appearance or reincidence of stroke.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Caspase 3/sangue , Caspase 8/sangue , Mediadores da Inflamação/sangue , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Superóxido Dismutase/genética , Fator de Necrose Tumoral alfa/sangue , Acetilcolinesterase/sangue , Idoso , Apoptose , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Crônica , Dano ao DNA , Regulação para Baixo , Feminino , Proteínas Ligadas por GPI/sangue , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Nitratos/sangue , Nitritos/sangue , Estresse Nitrosativo , Fenótipo , Prognóstico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/enzimologia
12.
Gynecol Obstet Invest ; 83(6): 576-585, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30071521

RESUMO

BACKGROUND/AIMS: To identify the role of serum caspase 3, Annexin A2 (ANXA2), and Soluble Fas Ligand (sFasL) levels in the prediction of endometriosis severity. METHODS: The study was performed on 90 women who were candidates for laparoscopic surgery due to endometrioma or any other benign ovarian cysts detected by ultrasound examination, pelvic pain, or infertility. The control group comprised 29  patients. The second group comprised 29 patients with stage I-II endometriosis and the third group comprised 30 patients with stage III-IV endometriosis. RESULTS: Significant differences were detected between the control and stage III-IV endometriosis groups and between stage I-II and stage III-IV endometriosis groups in terms of caspase-3 levels (both, p < 0.001), ANXA2 levels (p = 0.007 and p = 0.002), and sFasL levels (p = 0.022 and p = 0.044). After receiver operating characteristic analysis, the area under curve was 93% (95% CI 57-82) at 10.7 ng/mL cut-off level for caspase-3 with 90% sensitivity and 87% specificity. CONCLUSION: Serum caspase-3 level may be a reliable predictor of endometriosis severity.


Assuntos
Anexina A2/sangue , Caspase 3/sangue , Endometriose/sangue , Proteína Ligante Fas/sangue , Adolescente , Adulto , Endometriose/patologia , Feminino , Humanos , Laparoscopia , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Adulto Jovem
13.
Naunyn Schmiedebergs Arch Pharmacol ; 391(9): 945-952, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29862426

RESUMO

Peripheral nervous system neurotoxicity is the most problematic complication of cisplatin treatment. In this study, we have addressed the possible neuroprotective effect of canagliflozin on cisplatin-induced peripheral neurotoxicity in rats. Rats were randomly allocated into the following: control (vehicle) group, received hydhroxypropyl methyl cellulose; cisplatin group, injected cisplatin 2 mg/kg intraperitoneal, twice a week for 5 consecutive weeks; canagliflozin-cisplatin of received canagliflozin, 10 mg/kg/day by gavage and cisplatin in the same schedule like cisplatin group. Thermal nociception and rotarod performance were assessed. Malondialdehyde (MDA), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), and caspase 3 were determined in serum. Hematoxylin and eosin (H&E) and immunohistochemical stained sciatic nerve sections were examined. Cisplatin induced thermal hypoalgesia and decreased rotarod performance as well as GSH serum level while increased MDA, TNF-α, and caspase-3 serum levels with atrophy and fragmentation of the nerve fibers with decreased expression of myelin basic protein. Canagliflozin prevented thermal hypoalgesia and improved rotarod performance with increment in GSH serum level while decreased MDA, TNF-α, and caspase-3 levels as well as prevented fragmentation of the nerve fibers and enhanced myelin basic protein expression in relation to cisplatin group. Canagliflozin attenuates the neurotoxic effect of cisplatin through anti-inflammatory and anti-oxidant actions as well as inhibition of apoptosis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Canagliflozina/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos , Apoptose/efeitos dos fármacos , Canagliflozina/farmacologia , Caspase 3/sangue , Cisplatino , Glutationa/sangue , Masculino , Malondialdeído/metabolismo , Síndromes Neurotóxicas/sangue , Doenças do Sistema Nervoso Periférico/sangue , Substâncias Protetoras/farmacologia , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
14.
Am J Phys Med Rehabil ; 97(11): 825-831, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29863586

RESUMO

OBJECTIVE: Strenuous exercise can induce apoptosis in a variety of tissues. We investigated the effects of creatine loading on apoptosis markers after downhill running. DESIGN: Twenty-two middle-aged men were randomly assigned to either a creatine or a placebo group. Crossover design, double-blind controlled supplementation was performed using 20 g/d(-1) of creatine or maltodextrin for 7 days. Downhill running (12% incline) at 70% of heart rate maximum for 40 mins was performed on the eighth day. Blood samples were taken on the day before supplementation, after supplementation and after running. RESULTS: There were no significant changes in the caspase-3, caspase-9, p53, Bax, and IGF-1 concentrations from presupplementation to postsupplementation in both groups of creatine and placebo (P > 0.05). There were significant increases (P < 0.05) in serum caspase-3, caspase-9, p53, and Bax after running in the placebo group. These markers were not noticeably changed in the creatine group (P > 0.05). Bcl-2 was unchanged in the placebo group but substantially increased (P < 0.05) in the creatine group. No significant changes were observed in IGF-1 concentration after running comparing to prerunning in both groups (P > 0.05). Lactate levels increased similarly in both groups (P < 0.05). CONCLUSIONS: The findings indicate that creatine supplementation could prevent exercise-induced apoptotic markers.


Assuntos
Apoptose/fisiologia , Creatina/farmacologia , Suplementos Nutricionais , Corrida/fisiologia , Biomarcadores/sangue , Caspase 3/sangue , Caspase 9/sangue , Estudos Cross-Over , Método Duplo-Cego , Genes bcl-2 , Genes p53 , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Proteína X Associada a bcl-2/sangue
15.
Med Glas (Zenica) ; 15(2): 87-92, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29790482

RESUMO

Aim To investigate the lipid membranes of rat enterocytes in chronic carrageenan-induced gastroenterocolitis accompanied by the activation of apoptotic processes. Methods Steady-state fluorescence spectroscopy: a study by fluorescent probes - by ortho-hydroxy derivatives of 2,5-diaryl-1,3- oxazole. Activity of apoptosis signal-regulating kinase 1 and poly (ADP-ribose) polymerase in small intestinal homogenates, blood serum levels of matrix metalloproteinase-2 and caspase-3 and the level of DNA fragmentation in small intestinal homogenates were determined. Results Biochemical analysis revealed that an activation of apoptotic processes occurred in the intestinal epithelium of rats during chronic carrageenan-induced gastroenterocolitis. The fluorescence probes showed that activation of apoptotic processes in carrageenan-induced gastroenterocolitis was accompanied by changes in polar regions of rat enterocyte membranes, while no changes were revealed in more hydrophobic regions of the membranes. Conclusion The increase in hydration of membranes was attributed to the activation of the apoptosis of enterocytes. It has been shown that a fluorescent probe (2-(2'-hydroxyphenyl)-5-phenyl-1,3-oxazole) can be used for the detection of apoptosis of enterocytes.


Assuntos
Apoptose , Carragenina/efeitos adversos , Membrana Celular/efeitos dos fármacos , Enterocolite/fisiopatologia , Enterócitos/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Animais , Caspase 3/sangue , Membrana Celular/química , Fragmentação do DNA , Enterocolite/induzido quimicamente , Enterocolite/metabolismo , Enterócitos/citologia , Enterócitos/metabolismo , Feminino , Corantes Fluorescentes , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/fisiopatologia , Mucosa Intestinal/metabolismo , Intestinos/citologia , MAP Quinase Quinase Quinase 5/metabolismo , Metaloproteinase 2 da Matriz/sangue , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos
16.
Cardiorenal Med ; 8(3): 208-216, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29847820

RESUMO

BACKGROUND: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Its pathophysiology is complex and not completely understood. In this study, we examined the role of apoptosis and the caspase pathways involved. MATERIAL AND METHODS: We enrolled 40 acute heart failure (AHF) patients, 11 of whom developed AKI characterizing CRS type 1. We exposed the human cell line U937 to plasma from the CRS type 1 and AHF groups and then we evaluated apoptotic activity by annexin-V evaluation, determination of caspase-3, -8 and -9 levels, and BAX, BAD, and FAS gene expression. RESULTS: We observed significant upregulation of apoptosis in monocytes exposed to CRS type 1 plasma compared to AHF, with increased levels of caspase-3 (p < 0.01), caspase-9 (p < 0.01), and caspase-8 (p < 0.03) showing activation of both intrinsic and extrinsic pathways. Furthermore, monocytes exposed to CRS type 1 plasma had increased gene expression of BAX and BAD (intrinsic pathways) (p = 0.010 for both). Furthermore, strong significant correlations between the caspase-9 levels and BAD and BAX gene expression were observed (Spearman ρ = - 0.76, p = 0.011, and ρ = - 0.72, p = 0.011). CONCLUSION: CRS type 1 induces dual apoptotic pathway activation in monocytes; the two pathways converged on caspase-3. Many factors may induce activation of both intrinsic and extrinsic apoptotic pathways in CRS type 1 patients, such as upregulation of proinflammatory cytokines and hypoxia/ischemia. Further investigations are necessary to corroborate the present findings, and to better understand the pathophysiological mechanism and consequent therapeutic and prognostic implications for CRS type 1.


Assuntos
Apoptose , Síndrome Cardiorrenal/sangue , Síndrome Cardiorrenal/patologia , Caspases/sangue , Monócitos/patologia , Idoso , Idoso de 80 Anos ou mais , Síndrome Cardiorrenal/enzimologia , Caspase 3/sangue , Caspase 8/sangue , Caspase 9/sangue , Ativação Enzimática , Proteína Ligante Fas/genética , Feminino , Expressão Gênica , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Células U937 , Proteína X Associada a bcl-2/genética , Proteína de Morte Celular Associada a bcl/genética
17.
Eur J Pharmacol ; 828: 135-145, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29608898

RESUMO

Elevated blood glucose and insulin resistance are triggering factors for non-alcoholic steatohepatitis (NASH). We investigated the effects of the Sodium Glucose co-Transporter 2 (SGLT2) inhibitor canagliflozin on NASH development in rats with type 2 diabetes mellitus as well as the possible underlying mechanisms and for the first time the effect of canagliflozin on the hepatic zinc-α2-glycoprotein (ZAG) levels. Rats were treated with nicotinamide and streptozotocin to reduce the insulin secretory capacity then fed high fat diet for 8 weeks. The diabetic high fat diet rats were divided into three groups; untreated group, canagliflozin 10 mg/kg treated group and canagliflozin 20 mg/kg treated group during this period. The elevated blood glucose and glycated haemoglobin (HbA1c) levels in the diabetic high fat diet rats were significantly reduced by canagliflozin. Moreover, the diabetic high fat diet induced NASH development as evidenced by liver weight gain, hepatic lipid accumulation and low hepatic ZAG expression as well as increased serum alanine aminotransferase; all these changes were reversed in rats treated with canagliflozin. Additionally, canagliflozin succeeded to upregulate the hepatic ZAG levels in both normal and diabetic high fat fed rats, lower the serum and hepatic inflammatory cytokines levels as well as lower the serum caspase-3 levels and enhanced hepatic Bcl-2 expression. Also, canagliflozin attenuated hepatic oxidative stress and elevated the antioxidant enzymes activity as well as the total antioxidant capacity. All these effects of canagliflozin were dose dependant. CONCLUSION: SGLT2 inhibitor-canagliflozin- has beneficial effects in treatment of NASH associated with diabetes mellitus.


Assuntos
Canagliflozina/farmacologia , Proteínas de Transporte/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Glicoproteínas/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Regulação para Cima/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Caspase 3/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Jejum/sangue , Hemoglobina A Glicada/metabolismo , Insulina/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
18.
Medicine (Baltimore) ; 97(12): e0172, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29561429

RESUMO

The aims of this study were to investigate the interplay between autophagy and apoptosis and to investigate the association between both of autophagy and apoptosis and vitamin D and its receptor in hepatitis C virus (HCV) viral infection and its implication in the progression into hepatocellular carcinoma (HCC).A cross-sectional study where serum levels of microtubule-associated protein 1A/1B-light chain 3 (LC3); marker of autophagy, caspase-3; marker of apoptosis, vitamin D3 and vitamin D receptor (VDR) were measured in healthy subjects as well as HCV and HCV-HCC patients using enzyme-linked immunosorbent assay technique.Collectively, the liver profile revealed hepatic dysfunctions in HCV patients with or without HCC. A significant reduction in the serum concentration levels LC3 and caspase-3 were observed referring to the down regulation of autophagy and host-mediated apoptosis in HCV patients with or without HCC. Deficiency of vitamin D and decreased levels of its receptor were observed in HCV and HCV-HCC patients.The perturbation in vitamin D/VDR axis, which modulates both of autophagy and apoptosis in HCV infection, may point out to its involvement and implication in the pathogenesis of HCV infection and the development of HCV-related HCC. Therefore, supplementation with vitamin D may not be the only solution to restore the vital biological functions of vitamin D but VDR-targeted therapy may be of great importance in this respect.


Assuntos
Carcinoma Hepatocelular/sangue , Hepatite C/sangue , Neoplasias Hepáticas/sangue , Deficiência de Vitamina D/sangue , Apoptose/fisiologia , Autofagia/fisiologia , Biomarcadores/sangue , Carcinoma Hepatocelular/complicações , Caspase 3/sangue , Colecalciferol/sangue , Estudos Transversais , Hepacivirus , Hepatite C/complicações , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/complicações , Proteínas Associadas aos Microtúbulos/sangue , Receptores de Calcitriol/sangue , Albumina Sérica/metabolismo , Deficiência de Vitamina D/complicações
19.
Int Urol Nephrol ; 50(6): 1171-1180, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29368247

RESUMO

PURPOSE: The study was processed to investigate the effect of astaxanthin (AST; 3,3-dihydroxybeta, beta-carotene-4,4-dione) on the acute kidney injury induced by iohexol and the relationship with SIRT1/FOXO3a signal pathway. METHODS: Thirty male Sprague Dawley rats were randomly divided into five groups as follows: control group (CON; olive oil only), contrast media group, astaxanthin control group (100 mg/kg), low astaxanthin dose group (LAG, 50 mg/kg) and high astaxanthin dose group (HAG, 100 mg/kg). As followed, serum creatinine (SCr), blood urea nitrogen (BUN), the oxidative stress markers and apoptosis-related proteins were detected. Human proximal tubular epithelial cells (HK-2) were cultured in DMEM/F12 medium in vitro and then randomly divided into appropriate experimental groups: normal group (N), dimethyl sulfoxide (DMSO), iohexol group (I), iohexol + (1.0, 10.0 µmol/L) astaxanthin group (I + LAST; I + HAST), iohexol + SIRT1 inhibitors (nicotinamide) group (NA) and iohexol + si-RNA FOXO3a group (si-RNA FOXO3a); when cultured for 24 h, cell proliferation ability was tested by cell counting kit (CCK-8), reactive oxygen species (ROS) were detected by flow cytometry and the expression of SIRT1 and FOXO3a were observed using western blot. RESULTS: At the end of the experiment, the levels of SCr, BUN and malondialdehyde (MDA) were all increased in the CM group. The LAG and HAG reduce superoxide anion (SOD) activity, catalase (CAT) activity, glutathione peroxidase (GPx) activity and glutathione (GSH) content, as well as SCr and BUN level. Moreover, apoptosis-associated proteins, caspase 3 p17, bax and bcl-2 were upregulated. In HK-2 cells, after adding iohexol, proliferation and intracellular ROS levels were significantly increased. Using astaxanthin in advance after the intervention, the result is opposite. SIRTl inhibitors NA can reduce the expression of SIRTl and decrease the expression of FOXO3a protein. Si-RNA FOXO3a reduces the expression of FOXO3a but had no significant effect on the expression of SIRT1. CONCLUSIONS: Our study demonstrates that the intervention of astaxanthin could attenuate the oxidative stress and apoptosis in contrast-induced acute kidney injury (CI-AKI), and the SIRT1/FOXO3a pathway participates in the contrast-induced apoptosis of HK-2 cells. Finally, astaxanthin reduces CI-AKI by suppression of apoptosis, which may be through inhibition of SIRT1/FOXO3a pathways.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Proteína Forkhead Box O3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Lesão Renal Aguda/sangue , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Caspase 3/sangue , Catalase/sangue , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Meios de Contraste/efeitos adversos , Creatinina/sangue , Células Epiteliais , Proteína Forkhead Box O3/genética , Glutationa/sangue , Glutationa Peroxidase/sangue , Humanos , Iohexol/efeitos adversos , Túbulos Renais Proximais/citologia , Masculino , Malondialdeído/sangue , Niacinamida/farmacologia , Peptídeos/sangue , Proteínas Proto-Oncogênicas c-bcl-2/sangue , RNA Interferente Pequeno/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/sangue , Complexo Vitamínico B/farmacologia , Xantofilas/farmacologia , Xantofilas/uso terapêutico , Proteína X Associada a bcl-2/sangue
20.
Acta Medica (Hradec Kralove) ; 61(4): 144-149, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30664447

RESUMO

BACKGROUND: Topiramate (TPM) decreases cytokine release and generation of reactive oxygen species (ROS). Cytokine and endothelin-1 (ET-1) secretion and ROS formation play an important role in ischemia-reperfusion (I/R) injury. We aimed to evaluate whether TPM prevents damage occurring in lung tissue during I/R. MATERIALS AND METHODS: A total of 27 Wistar albino rats were divided into three groups of nine. To the I/R group, two hours of ischemia via infrarenal abdominal aorta cross-ligation and then two hours of reperfusion process were applied. TPM (100 mg/kg/day) orally for seven days was administered in the TPM treatment group. After the last dose of TPM treatment, respectively, two hours of ischemia and two hours of reperfusion were applied in this group. RESULTS: Tumor necrosis factor-alpha (TNF-α) (p < 0.05), malondialdehyde (MDA) (p < 0.05), myeloperoxidase (MPO) (p < 0.05) and ET-1 (p < 0.05) levels of TPM treatment group's lung tissue were significantly lower than for the I/R group. Caspase-3 and histopathological damage were rather lower than that of the I/R group. CONCLUSIONS: During I/R, lung damage occurs due to excessive TNF-α and ET-1 release and ROS generation. TPM could well reduce development of lung damage by decreasing cytokine and ET-1 release and levels of ROS produced.


Assuntos
Lesão Pulmonar/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Topiramato/farmacologia , Animais , Aorta Abdominal , Biomarcadores/sangue , Caspase 3/sangue , Ligadura , Masculino , Malondialdeído/sangue , Peroxidase/sangue , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
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