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1.
Arab J Sci Eng ; 48(1): 1031-1040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36321067

RESUMO

Thiophene-containing compounds have antiviral properties and may be among the drugs tested for the treatment of COVID-19 diseases. In order to better understand the molecular definition of the 1-(2´-Thiophen)-2-propen-1-one-3-(2,3,5-trichlorophenyl) molecule from thiophene-containing compounds, the physico-chemical (molecular structure analysis, spectroscopic properties, boundary orbital analysis) mechanisms underlying the protein-ligand interaction should be examined in detail. For this reason, geometric parameters, IR and UV-vis spectra, conformational analysis, electronic, NBO and NLO properties, molecular electrostatic potential map and Mulliken charge distributions of the TTCP molecule were investigated theoretically using DFT theory in the Gaussian program. Accordingly, molecular docking calculations with COVID-19 main protease (PDB 5R7Y) were performed to determine the pharmaceutical activities of the TTCP molecule against coronavirus diseases.

2.
Int J Exp Pathol ; 100(5-6): 330-336, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31777145

RESUMO

One of the most important causes of visual loss (blindness) is glaucoma, which occurs due to the degeneration of the ganglion cells in retina. It has been shown that hydrogen sulphide (H2 S) acts an antioxidant, neuroprotective and neuromodulator and provides protection against oxidative stress and apoptosis. This study aims to examine through which apoptotic pathway H2 S acts in experimental glaucoma model. Twenty-two male wistar albino rats were used in this study. Group 1 (n = 6, control group): Intravitreal saline was given in the third week without inducing ocular hypertension (OHT) with laser photocoagulation. Group 2 (n = 8): After the induction of OHT with laser photocoagulation, intravitreal saline was given in the third week. Group 3 (n = 8): After the induction of OHT with laser photocoagulation, intravitreal H2 S's donor sodium hydrosulphide (NaSH) 100 nmol/L was given in the third week. At the end of the 6th week, the eyes of the rats were sacrified under anaesthesia and extracted and then routine tissue follow-up was undertaken. Besides haematoxylin & eosin (H&E) staining, Bax, Bcl-2, p53 and caspase-3 activation were examined immunohistochemically in the retina and the cornea. This showed that ocular hypertension caused apoptosis through the intrinsic pathway, due to Bax and caspase-3 activation, in both retina and cornea, and that this led to DNA damage due to p53 activation. Also, we found that H2 S exposure in glaucoma distinctly suppressed Bax, caspase-3 and p53 activations in retina but that it has a limited effect on the cornea. According to these results, glaucoma caused apoptosis in the retina through intrinsic pathway, and the damage to the retina could be compensated partially by H2 S but would have limited on the cornea.


Assuntos
Apoptose/efeitos dos fármacos , Córnea/diagnóstico por imagem , Glaucoma/tratamento farmacológico , Sulfeto de Hidrogênio/farmacologia , Substâncias Protetoras/farmacologia , Retina/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Córnea/metabolismo , Córnea/fisiopatologia , Glaucoma/metabolismo , Glaucoma/fisiopatologia , Sulfeto de Hidrogênio/administração & dosagem , Sulfeto de Hidrogênio/uso terapêutico , Injeções Intravítreas , Masculino , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Wistar , Retina/metabolismo , Retina/fisiopatologia
3.
Adv Med Sci ; 63(2): 347-352, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30092503

RESUMO

PURPOSE: Folic acid is an essential vitamin participating in DNA synthesis and repair. Recently folic acid has been shown to stimulate DNA-repair capacity in dermal fibroblasts in response to injury. Thus, the present study aimed to investigate the effects of topical folinic acid, a 5-formyl derivative of tetrahydrofolic acid, on wound healing using rat wound model. MATERIALS AND METHODS: A rat wound model was established, and the wound healing was evaluated by macroscopic and histological analyses among vehicle control, 2.5% folinic acid, 1% folinic acid, and dexpanthenol treatment groups. While an image-analysis program was used to evaluate macroscopic wound closure, connective tissue properties, mast cell numbers, and the expressions of matrix metalloproteinase 1 (MMP-1) and 9 (MMP-9) were evaluated by microscopy. RESULTS: The 2.5% folinic acid-treated group exhibited enhanced wound healing by increased reepithelialization, neo-vessel formation, inflammatory cell migration, collagen deposition and progressive mast cell increase. Furthermore, 2.5% folinic acid induced higher expressions of MMP-1 and MMP-9. CONCLUSIONS: Folinic acid enhances both macroscopic and microscopic wound healing in rat wound model.


Assuntos
Leucovorina/administração & dosagem , Leucovorina/farmacologia , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Derme/patologia , Modelos Animais de Doenças , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/patologia , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Ratos Sprague-Dawley
4.
Drug Des Devel Ther ; 12: 1347-1352, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29861626

RESUMO

AIM: The aim of this study was to investigate the effects of levosimendan and thymoquinone (TQ) on lung injury after myocardial ischemia/reperfusion (I/R). MATERIALS AND METHODS: Twenty-four Wistar albino rats were included in the study. The animals were randomly assigned to 1 of 4 experimental groups. In Group C (control group), left anterior descending artery was not occluded or reperfused. Myocardial I/R was induced by ligation of the left anterior descending artery for 30 min, followed by 2 h of reperfusion in the I/R, I/R-levosimendan (24 µg/kg) (IRL) group, and I/R-thymoquinone (0.2 mL/kg) (IRTQ) group. Tissue samples taken from the lungs of rats were histochemically stained with H&E and immunohistochemically stained with p53, Bcl 2, Bax, and caspase 3 primer antibodies. RESULTS: Increased expression of p53 and Bax was observed (4+), especially in the I/R group. In IRTQ and IRL groups, expression was also observed at various locations (2+, 3+). H&E staining revealed that that the lungs were severely damaged and the walls of the alveoli were too thick, the number of areas examined was increased during the evaluation. Caspase 3 expression was observed to be at an (1+, 2+) intensity that was usually weak and diffuse in multiple areas. Bcl 2 was not found to be expressed in any of the tissues. H&E staining revealed that that the lungs were severely damaged in the I/R group, with the walls of the channels and alveoli thickened and edematous, and also an intense inflammatory cell migration was observed. Immunohistochemical staining was more prominent in inflammatory areas and structures around the terminal bronchioles. CONCLUSION: The findings in our study have shown that administration of levosimendan and TQ during I/R increases expression of caspase 3, p53, and Bax in lung tissue and has a protective effect on lung as distant organ. We suggest that findings of this study be elucidated with further large-scale clinical studies.


Assuntos
Benzoquinonas/uso terapêutico , Hidrazonas/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Piridazinas/uso terapêutico , Animais , Benzoquinonas/administração & dosagem , Hidrazonas/administração & dosagem , Imuno-Histoquímica , Injeções Intraperitoneais , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Piridazinas/administração & dosagem , Ratos , Ratos Wistar , Simendana , Proteína X Associada a bcl-2/análise , Proteína X Associada a bcl-2/biossíntese
5.
Ann Ital Chir ; 87: 271-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27346180

RESUMO

BACKGROUND: Severe local and systemic tissue injuries can occur after restoration of tissue oxygenation which is also known as reperfusion injury. Our objective was to investigate the possible protective effects of melatonin against IR damage in hepatic tissue following infrarenal aortic occlusion. METHODS: A total of twenty-one male Wistar-albino rats separated into three groups as follows: Group I: Laparotomy and dissection of the infrarenal abdominal aorta (AA) were concurrently performed. Group II: About 1 ml of 0.9% saline was intraperitoenally administered 30 min before and after the occlusion operation. After laparotomy and dissection, infrarenal AA was clamped for 30 minutes and then was exposed to two hours of reperfusion. Group III: The melatonin was administered 30 min before clamping of the infrarenal AA then 30 min of ischemia and two hours of reperfusion was applied. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels were remarkably higher in IR group, when compared with the sham group, and the laboratory tests returned to normal levels in IR+MEL group after treatment. Although serum IL-1ß, IL-6, IL-18, TNF-α, and IFN- γ levels have decreased in treatment group following melatonin administration, this decrement was statistically significant for serum IL-18, TNF-α, and IFN- γ parameters compared with the IR group. Serum levels of TOC and OSI were decreased and tissue levels of TAC were increased by melatonin. CONCLUSION: As a result of this study, it can be suggested that melatonin has antioxidant, anti-inflammatory and hepatoprotective effects in case of IR. KEY WORDS: Aortic occlusion, Injury, Ischemia/Reperfusion, Liver, Melatonin.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Aorta Abdominal/cirurgia , Isquemia/complicações , Fígado/irrigação sanguínea , Melatonina/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores , Constrição , Citocinas/sangue , Avaliação Pré-Clínica de Medicamentos , Isquemia/etiologia , L-Lactato Desidrogenase/sangue , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/etiologia
6.
J Invest Surg ; 29(6): 389-398, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27142763

RESUMO

AIM: The purpose of this study was to evaluate the possible protective/therapeutic effects of aloe vera (AV) on ischemia-reperfusion injury (I/R) of spinal cord in rats. MATERIALS AND METHODS: A total of 28 Wistar Albino rats were divided into four random groups of equal number (n = 7). Group I (control) had no medication or surgery; Group II underwent spinal cord ischemia and was given no medication; Group III was administered AV by gastric gavage for 30 days as pre-treatment; Group IV was administered single dose intraperitoneal methylprednisolone (MP) after the ischemia. Nuclear respiratory factor-1 (NRF1), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were evaluated. Tissue samples were examined histopathologically and neuronal nitric oxide synthase (nNOS) and nuclear factor-kappa B (NF-κB) protein expressions were assessed by immunohistochemical staining. RESULTS: NRF1 and SOD levels of ischemia group were found to be lower compared to the other groups. MDA levels significantly increased after I/R. Treatment with AV and MP resulted in reduced MDA levels and also alleviated hemorrhage, edema, inflammatory cell migration and neurons were partially protected from ischemic injury. When AV treatment was compared with MP, there was no statistical difference between them in terms of reduction of neuronal damage. I/R injury increased NF-κB and nNOS expressions. AV and MP treatments decreased NF-κB and nNOS expressions. CONCLUSIONS: It was observed that aloe vera attenuated neuronal damage histopathologically and biochemically as pretreatment. Further studies may provide more evidence to determine the additional role of aloe vera in spinal cord ischemia reperfusion injury.


Assuntos
Fitoterapia , Preparações de Plantas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Avaliação Pré-Clínica de Medicamentos , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Distribuição Aleatória , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia
7.
Neurol Res ; 38(4): 364-72, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27078696

RESUMO

BACKGROUND AND AIM: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are one of the sources of adult stem cells being explored for potential use in repairing neurodegenerative disorders. In this study, it was aimed to investigate the useful effects of BM-MSCs therapy on the streptozotocin-induced neurodegeneration in rats. MATERIALS AND METHODS: Adult female Wistar rats were bilaterally injected intra-cerebroventricularly with streptozotocin (3 mg/kg) for neurodegeneration. Water maze tests were used to monitor spatial learning and memory. One or two intravenous injections of BM-MSCs were administrated to rat via the tail veins. At the end of the study, all rats were sacrificed for histological evaluation and immunohistochemistry. RESULTS: Streptozotocin group demonstrated a significant increase in escape latency in comparison with both control groups (Sham and Saline), whereas rats treated with BM-MSCs exhibited a decrease in escape latency in comparison with streptozotocin group. The percentage of time spent in the target quadrant and the mean number of platform crossings did not change in all the groups. BM-MSCs administration improved spatial learning but not memory. However, improvement in neuronal cells in hippocampal CA1 region was only observed in the rats treated with BM-MSCs twice as opposed to the rats treated with BM-MSCs once or with saline. CONCLUSIONS: In this study, mesenchymal stem cells therapy failed to improve the streptozotocin-induced neurodegeneration like Alzheimer's disease in rats.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Transplante de Células-Tronco Mesenquimais/métodos , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/cirurgia , Estreptozocina/toxicidade , Animais , Transtornos Cognitivos/etiologia , Modelos Animais de Doenças , Feminino , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Marcação In Situ das Extremidades Cortadas , Aprendizagem em Labirinto , Células-Tronco Mesenquimais/fisiologia , Doenças Neurodegenerativas/complicações , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Fatores de Tempo , Transfecção
8.
Drug Dev Res ; 77(1): 12-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26748675

RESUMO

Preclinical Research Trans-resveratrol has a wide range of biological effects that reflect its antioxidant, anti-inflammatory, anticarcinogenic and cardioprotective properties. This study was conducted to elucidate the potential role of resveratrol on hepatic inflammation and the apoptotic pathway components Bcl-2, Bax and p53 in a streptozotocin (STZ)-induced rat model of diabetes mellitus. Inflammatory and apoptotic biomarkers indicated a reduction in hepatic erythropoietin (1.26-fold) and increased asymmetric dimethylarginine (3.9-fold), visfatin (1.6-fold), inflammatory interleukins and TNF-α contents (approximately twofold each) in the diabetic animals. Induction of inducible nitric oxide synthase gene (2.04-fold) and protein expression (1.24-fold) was also observed. Immunohistochemical studies showed enhancement of the apoptotic biomarkers Bax and p53 in diabetic animals. STZ-induced diabetic male Wistar rats were treated with resveratrol (20 mg/kg/day i.p.). Resveratrol succeeded to recover most of these inflammatory and apoptotic elements. Therefore, inflammatory and apoptotic pathways were proved to be affected by STZ-induced diabetes in several aspects and resveratrol might contribute hepatoprotective effects as evidenced from this study.


Assuntos
Anti-Inflamatórios/administração & dosagem , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Fígado/imunologia , Estilbenos/administração & dosagem , Animais , Anti-Inflamatórios/farmacologia , Apoptose , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/patologia , Eritropoetina/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucinas/metabolismo , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Resveratrol , Estilbenos/farmacologia , Estreptozocina , Fator de Necrose Tumoral alfa/metabolismo
9.
Bosn J Basic Med Sci ; 15(4): 36-43, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26614850

RESUMO

Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (p<0.01), levels of MDA, NO, and inducible nitric oxide synthase (iNOS) positive cells (p<0.01, p<0.05, respectively), and increased SOD, GPx, and CAT activities (p<0.001, p<0.01, p<0.05, respectively) compared with the I/R group that did not receive ebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (p<0.01, p<0.05, p<0.001) and MDA and NO levels (p<0.05, p<0.01) and decreased SOD, GPx, and CAT activities (p<0.05) compared with the sham group. The results of this study suggest that ebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.


Assuntos
Azóis/uso terapêutico , Isquemia/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Compostos Organosselênicos/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Neuropatia Ciática/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Isquemia/patologia , Isoindóis , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Neuropatia Ciática/patologia
10.
J Surg Res ; 199(2): 393-401, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26163327

RESUMO

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a major complication in clinical practice. Previous studies suggest that statins have pleiotropic effects in addition to cholesterol-lowering effects. In this study, we aimed to investigate the hepatoprotective role of two different doses of simvastatin (SV) pretreatment in rats with experimental hepatic I/R injury. METHODS: Adult male Sprague-Dawley rats were divided into four groups (n = 7 in each group) :control, I/R, I/R with 2.5-mg/kg SV, and I/R with 5.0-mg/kg SV. Before hepatic I/R was induced, SV was injected intraperitoneally at doses of 2.5 and 5.0 mg/kg. After 45-min ischemia and a 60-min reperfusion period, the animals were euthanized, and liver tissues were excised. Tissue levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase, glutathione peroxidase, and catalase were measured. Liver tissues were also evaluated histopathologically and immunohistochemically. RESULTS: Histopathologic evaluation showed that 5.0-mg/kg SV reduced hepatic damage and apoptosis. Pretreatment with 5.0-mg/kg SV reduced malondialdehyde and nitric oxide levels (P < 0.01) and increased superoxide dismutase, glutathione peroxidase, and catalase activities significantly (P < 0.001, P < 0.01) in I/R with 2.5-mg/kg SV compared with I/R group. In addition, SV decreased Kupffer cell activation, and hypoxia-inducible factor-1α and vascular endothelial growth factor protein levels. CONCLUSIONS: The results of this study suggest that 5.0-mg/kg SV pretreatment may be protective against hepatic I/R injury. This effect can be achieved by antioxidant and antiapoptotic activities.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Sinvastatina/uso terapêutico , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Fígado/enzimologia , Fígado/patologia , Hepatopatias/patologia , Masculino , Distribuição Aleatória , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia
11.
Gene ; 570(2): 213-20, 2015 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-26071184

RESUMO

Diabetes mellitus is a heterogeneous metabolic disorder essentially characterized by deficiency of insulin secretion, insulin receptor or post-receptor events. This study aims to investigate the effects of resveratrol administration on the metabolic characteristics, hepatic functions, histopathological features and insulin signaling pathway components in streptozotocin induced diabetes. Male Wistar rats were randomly divided into four groups: (1) control/vehicle; (2) control/20mg/kg resveratrol; (3) diabetic/vehicle; and (4) diabetic/20mg/kg resveratrol. Histopathological examinations were carried out to reveal hepatic tissue damage and inflammation. In addition to hepatic glucose, lipid, insulin, ALT, AST, resistin and XOD contents, gene and protein expressions of insulin signaling pathway components such as insulin Rß, IRS-1, IRS-2, eNOS, PI3K, Akt, and FOXO3a were analyzed by qRT-PCR and Western blot. The rats in the diabetes group had significantly lower terminal body weight and hepatic insulin level, but significantly higher hepatic glucose, total cholesterol, triglyceride and resistin concentrations. Diabetes triggered the inflammatory process in the liver tissues that was evidenced by histopathological deformations and increase in the hepatic ALT and AST levels. Hepatic inflammation was considerably associated with insulin signaling pathway ever since a significant down-regulation of insulin signaling components; IRS-1, IRS-2, PI3K, Akt and mTOR have been identified in the diabetic group. To some extent, resveratrol treatment reversed the diabetes-induced changes in the liver tissues. Taken together, resveratrol partly improved hepatic dysfunction induced by diabetes. This may be due to the healing activity of resveratrol on insulin signaling pathway, resistin levels and hepatic glucose-lipid contents.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Inflamação/prevenção & controle , Insulina/metabolismo , Fígado/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Resveratrol , Estreptozocina
12.
J Korean Neurosurg Soc ; 57(3): 147-51, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25810852

RESUMO

OBJECTIVE: Neuroblastoma is one of common childhood tumors. Although its mortality is very high, there is no effective treatment yet. The aim of this project is to evaluate cytotoxic effects of melatonin (MLT) an endogen hormone and 13-cis retinoic acid (13-cis-RA) also named as isotretinoin an analogue of vitamin A on neuroblastoma SH-SY5Y cell line. METHODS: In this study, SH-SY5Y cell line was used. After cell culture, the cells were exposed to different doses of MLT and 13-cis-RA. 24 and 48 hours later. While the viabilities was estimated with MTT cell viability assay test, apoptotic indexes were calculated after staining with TUNEL based apoptosis kit. RESULTS: It was observed that MLT has very effective cytotoxic potential than 13-cis-RA on neuroblastoma cell line. At the same time, when MLT and 13-cis-RA were combined, this effect was potentiated. On the other hand, it was found that the effect of 13-cis-RA individually on neuroblastoma cells was very slight. CONCLUSION: We suggest that in the treatment of patient with neuroblastoma, MLT is very effective and also this effect can be augmented by combination with 13-cis-RA.

13.
Int. j. morphol ; 33(1): 255-261, Mar. 2015. ilus
Artigo em Inglês | LILACS | ID: lil-743794

RESUMO

Boron is an essential element for life and intake via different sources into the body. Because effects of boron and compounds on the body has not been studied enough especially in tissue level, we planned this study to evaluate the effects of borax the most intaken form of boron compound on different intraabdominal organs histologically and also clinically. 42 male rats divided into equal 7 groups and different toxicological doses consistent with its LD50 dose (5000 mg/kg/d) were administered by gavage except control and sham groups. In the study, 2 different kinds of borax one of which was produced for research and the other for agriculture but the same formulation, were used and their effects were also compared. As a result it was found that borax did not cause any histological changes in kidney, large intestine, liver and stomach in lower doses. But if doses were increased, a slightly inflammatory cell migration was detected without clinical signs in liver and large intestine. However, when a single very high dose of borax was administered, very high edema, inflammatory cell migration and neovascularization was observed and clinically 2 out of 6 rats died within 5 hours. We suggested that very high dose intake of borax may cause sudden death and also during long periods and higher dose intake may pave the way of inflammatory bowel diseases. At the same time, in boron related studies we advice that the kind of boron and also their source should be evaluated carefully and the most suitable compound should be chosen in case of faulty results.


El boro es un elemento esencial para la vida e ingresa a través de diferentes fuentes al cuerpo. Dado que los efectos del boro y sus compuestos en el cuerpo no se han estudiado lo suficiente, especialmente a nivel tisular, se planificó este estudio para evaluar sus efectos y la forma de consumo más común del compuesto de boro sobre diferentes órganos intraabdominales a nivel histológico y clínico. Cuarenta y dos ratas macho divididas en 7 grupos, con diferentes dosis toxicológicas de acuerdo con su dosis DL50 (5000 mg/kg/d) administradas por sonda, excepto en los grupos control y simulado. En el estudio fueron usados 2 tipos diferentes de boro, uno producido para la investigación y el otro para la agricultura, pero de la misma formulación, y sus efectos fueron comparados. Se encontró que el boro no causó cambios histológicos en el riñón, intestino grueso, hígado y estómago en dosis bajas. Sin embargo, al aumentar la dosis, se detectó una leve migración de células inflamatorias, sin signos clínicos, en el hígado e intestino grueso. Por otra parte, cuando se administró una sola dosis muy alta de boro, se observó un amplio edema, migración de células inflamatorias y neovascularización; clínicamente 2 de 6 ratas murieron dentro de 5 horas. Sugerimos que la ingesta de dosis muy altas de bórax pueden causar la muerte súbita, además la ingesta de dosis altas y durante periodos de tiempo prolongado puede causar enfermedades inflamatorias del intestino. Es recomendable que en los estudios relacionados con el boro, el tipo de boro así como su fuente sean evaluados cuidadosamente, eligiendo el compuesto más adecuado en caso de resultados erróneos.


Assuntos
Animais , Masculino , Ratos , Boro/toxicidade , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/patologia , Intestino Grosso/efeitos dos fármacos , Intestino Grosso/patologia , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Ratos Sprague-Dawley , Estômago/efeitos dos fármacos , Estômago/patologia
14.
Ann Surg Treat Res ; 88(2): 92-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25692120

RESUMO

PURPOSE: Severe local and systemic tissue damage called ischemia/reperfusion (IR) injury occurs during the period of reperfusion. Free oxygen radicals and proinflammatory cytokines are responsible for reperfusion injury. IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. The balance between IL-18 and IL-18BP has an important role in the inflammatory setting. The present study aimed to investigate whether IL-18BP had a protective role in remote organ hepatic IR injury. METHODS: Wistar-Albino rats were divided into three groups that contained seven rats. Group I (sham): Laparotomy and infrarenal abdominal aorta (AA) dissection were done but no clamping was done. Group II (I/R): The infrarenal AA was clamped by atraumatic microvascular clamp for 30 minutes and then was exposed to 90 minutes of reperfusion. Group III (IR + IL-18BP): 75 µg/kg of IL-18BP in 0.9% saline (1 mL) was administered 30 minutes before infrarenal AA dissection and clamping; 30 minutes of ischemia was applied and then was exposed to 90 minutes of reperfusion. RESULTS: Serum AST, ALT, and LDH levels were remarkably higher in IR group and returned to normal levels in treatment group. The proinflammatory cytokine levels had decreased in treatment group, and was statistically significant compared with the IR group. Serum levels of total oxidant status and oxidative stress index decreased and levels of total antioxidant status increased by IL-18BP. CONCLUSION: This study suggested that IL-18BP has antioxidant, anti-inflammatory and hepatoprotective effects in cases of IR with infrarenal AA induced liver oxidative damage.

15.
Food Chem ; 165: 555-9, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25038711

RESUMO

Mulberry pekmez can be adulterated in different ways either during the production process or after production is completed. To identify these adulterations, stable carbon isotope ratio analysis (SCIRA) was performed on the model examples prepared by adding saccharose syrup (SS), glucose syrup (GS) and high fructose corn syrup (HFCS) into two different pure mulberry pekmez samples in the ratios of 0%, 10%, 30% and 50%. The δ(13)C ratio of the pure mulberry pekmez was determined as -26.60‰ on average, the saccharose syrup as -24.80‰, the glucose syrup as -11.20‰ and the high-fructose corn syrup as -11.40‰. In identifying the adulteration made to pekmez, especially with the high-fructose corn syrup, which is obtained from corn starch, and with the glucose syrup, the δ(13)C ratio comes into prominence. However it remains impossible identify the adulterations made with the saccharose, which is obtained from beet sugar, or invert sugar syrups.


Assuntos
Carboidratos/análise , Isótopos de Carbono/análise , Contaminação de Alimentos/análise , Morus/química , Beta vulgaris/química , Carbono/análise , Contaminação de Medicamentos , Frutose/análise , Frutas/química , Glucose/análise , Sacarose/análise
16.
Mol Biol Rep ; 41(10): 6391-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25034890

RESUMO

Laparoscopic surgery techniques have been increasingly preferred to classic laparotomy by surgeons since 1987. However, this method may have some side effects on different intraabdominal organs including kidneys. The aim of this study is to evaluate the effects of different pressures of CO2 on p53 related apoptosis in kidneys. Totally 24 male rats were divided into four equal groups. CO2 is insufflated into rats' intraabdominal cavity in two different pressures of 10 and 20 mmHg during 1 h. However, in sham group, only cannula was inserted, but no gas was insufflated. After 1 h, 30 min reperfusion was applied. At last, the kidneys were excised and p53 expression and apoptosis were evaluated immunohistochemically. All the data revealed that the number of apoptotic cell in kidney' tubular cells significantly increases in proportion to CO2 pressure level. On the other hand, p53 expression was detected only in the highest pressure. Because the low CO2 pressured group' rats had no p53 expression in kidneys, we suggest that this method can be safely used for abdominal surgery. At the same time, increasing in the number of apoptotic cells parallel to pressure also suggest that CO2 pressure level and application time are very important parameters during CO2 pneumoperitoneum.


Assuntos
Apoptose , Rim/metabolismo , Pneumoperitônio/metabolismo , Pneumoperitônio/fisiopatologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/genética , Imuno-Histoquímica , Rim/patologia , Masculino , Pneumoperitônio/etiologia , Ratos , Proteína Supressora de Tumor p53/genética
17.
J Surg Res ; 187(1): 162-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24176208

RESUMO

PURPOSE: The aim of this study was to investigate the effects of iloprost (IL) on ischemia-reperfusion injury in a rodent model. MATERIALS AND METHODS: Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in group S (Sham). Ischemia-reperfusion group (group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 min. The iloprost group (group IL) received intravenous infusion of IL 0.5 ng/kg/min, without I/R. Group I/R + IL received intravenous infusion of IL 0.5 ng/kg/min immediately after 2 h period of ischemia. At the end of the reperfusion period, all rats were killed under anesthesia and skeletal muscle samples of lower extremity were harvested for biochemical and histopathologic analyses. RESULTS: Tissue levels of endothelial nitric oxide were significantly higher in I/R groups than those in groups S and IL. The heat shock protein 60 levels were higher in group I/R than the other groups. But the heat shock protein 60 levels in group I/R + IL were found to be similar with the groups S and IL. Malondialdehyde levels were significantly higher in group I/R. On the other hand, in group I/R + IL, malondialdehyde levels were higher than those in groups S and IL but lower than those in group I/R. Superoxide dismutase (SOD) enzyme activities were found to be significantly lower in group I/R than the other groups. Also in group I/R/I, the SOD enzyme activities were higher than those in group I/R. But, in group I/R + IL, SOD levels were found to be higher than those in group I/R but lower than those in groups S and IL. CONCLUSIONS: These results indicate that IL has protective effects on I/R injury in skeletal muscle in a rodent model.


Assuntos
Iloprosta/farmacologia , Músculo Esquelético/irrigação sanguínea , Traumatismo por Reperfusão/tratamento farmacológico , Vasodilatadores/farmacologia , Animais , Aorta Abdominal , Chaperonina 60/metabolismo , Modelos Animais de Doenças , Malondialdeído/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Distribuição Aleatória , Ratos , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismo
18.
Mol Biol Rep ; 40(10): 5733-40, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24057237

RESUMO

The aim of the present study was to evaluate the protective effects of the NF-кB inhibition with pyrrolidine-dithiocarbamate (PDTC) in ischemia-reperfusion (I/R) injury in the rat bladder. Twenty-four Sprague-Dawley male rats were divided into three groups. Group I; (n = 8) control, group II; (n = 8) I/R group; group III (n = 8) I/R and PDTC treatment. Superoxide dismutase (SOD), catalase (CAT), and gluatathione-S-transferase (GST) enzymes was studied in bladder tissue. Lipid peroxidation (as TBARS) levels in tissue homogenate were measured with thiobarbituric acid reaction. All the slides were stained with NF-кB, p53 and HSP60 immunohistochemistry for detection genome destruction and tissue stress, respectively. Our results show that the mean TBARS levels were significantly higher in group II (p < 0.05). The TBARS levels were significantly decreased in group III compared with the group II (p < 0.05). CAT, SOD and GST activities were decreased in group II, but these enzymes levels were significantly increased in group III according to the group II (p < 0.05). Under microscopic evaluation NF-кB expression increased significantly in group II compared to the group I (p < 0.05) and then decreased in group III (p < 0.05). HSP60 and p53 expression in group II was increased significantly compared with group I. Under microscopic evaluation we detected that HSP60 and p53 expression was increased significantly in group II compared with group I. In group III PDTC administration was decreased the HSP60 and p53 expression, this difference was statistically significant (p < 0.05). The results of the present study have demonstrated that NF-кB inhibition with PDTC protects and provides beneficial effects on ischemia/reperfusion stress related bladder tissue destruction.


Assuntos
NF-kappa B/antagonistas & inibidores , Substâncias Protetoras/uso terapêutico , Pirrolidinas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Tiocarbamatos/uso terapêutico , Bexiga Urinária/irrigação sanguínea , Bexiga Urinária/patologia , Animais , Catalase/metabolismo , Glutationa/metabolismo , Masculino , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Pirrolidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Tiocarbamatos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Bexiga Urinária/efeitos dos fármacos
19.
Food Chem ; 138(2-3): 1629-32, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23411291

RESUMO

Honey can be adulterated in various ways. One of the adulteration methods is the addition of different sugar syrups during or after honey production. Starch-based sugar syrups, high fructose corn syrup (HFCS), glucose syrup (GS) and saccharose syrups (SS), which are produced from beet or canes, can be used for adulterating honey. In this study, adulterated honey samples were prepared with the addition of HFCS, GS and SS (beet sugar) at a ratio of 0%, 10%, 20%, 40% and 50% by weight. (13)C/(12)C analysis was conducted on these adulterated honey samples using an isotope ratio mass spectrometer in combination with an elemental analyser (EA-IRMS). As a result, adulteration using C(4) sugar syrups (HFCS and GS) could be detected to a certain extent while adulteration of honey using C(3) sugar syrups (beet sugar) could not be detected. Adulteration by using SS (beet sugar) still has a serious detection problem, especially in countries in which beet is used in manufacturing sugar. For this reason, practice and analysis methods are needed to meet this deficit and to detect the adulterations precisely in the studies that will be conducted.


Assuntos
Contaminação de Alimentos/análise , Glucose/análise , Mel/análise , Espectrometria de Massas/métodos , Sacarose/análise , Isótopos de Carbono/química
20.
Exp Ther Med ; 4(2): 344-348, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23139723

RESUMO

We aimed to determine whether rotenone treatment prevents induced ischemia/reperfusion (I/R) damage in rat bladders by detecting inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels by real-time PCR (RT-PCR). A total of 18 Sprague-Dawley albino rats were used in this experiment. The experimental groups each consisted of 6 rats and were treated as follows: group I, control; group II, I/R; group III, rotenone + I/R. In the control group, the rat bladders were removed by lower abdominal incision without any procedure. In the I/R group, 1 h prior to the ischemia 1 cc physiological serum was administered and the abdominal aortas were clamped for 1 h to achieve bladder ischemia. Following the ischemia, reperfusion was induced for 1 h and the bladders were removed. In the rotenone + I/R group, the rats were treated with 25 mg/kg rotenone intraperitoneally. The iNOS and COX-2 mRNA levels in each group were detected using RT-PCR. In the I/R group, the COX-2 levels in the bladder tissue were higher compared with the control group (P<0.05). The COX-2 levels in the rotenone-treated group were statistically lower compared with the I/R group (P<0.01). Vascularization and edema were markedly increased in the I/R group. Following rotenone treatment these were abrogated inversely to inflammation. Although iNOS levels were slightly higher in the I/R group compared with the control group, iNOS levels did not decrease and no significant difference was observed between the groups with regard to rotenone treatment (P>0.05). We suggest that rotenone may be used clinically to treat I/R damage due to its diminishing effect on COX-2 levels.

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