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In our study, the protective role of synthetic aromatase inhibitors anastrozole (ANS), letrozole (LTZ) and exemestane (EXM) and natural aromatase inhibitors resveratrol (RSV) and apigenin (APG) against testicular failure caused by exposure to Bisphenol A (BPA) was investigated. The epididymal sperm concentration, sperm motility and sperm morphology were determined. Oxidative stress and inflammatory response parameters were examined and histological examinations were performed in testicular tissues. Our results revealed that BPA exposure decreased serum testosterone and estrogen levels, increased FSH and LH levels (p < 0.05). BPA has been found to increase oxidative stress and inflammatory response and disrupt the histological structure. Also, BPA exposure decreased testicular weight, epididymal sperm concentration and motility, and increased abnormal sperm rate (p < 0.05). These results show that ANS, LTZ and RSV treatments reduce the BPA-induced testicular damage.
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Cancer is still one of the most important diseases that have a high mortality rate around the world. The management of cancer involves many procedures, which include surgery, radiotherapy, and chemotherapy. Drug resistance in cancer chemotherapy is considered one of the most important problems in clinical oncology. A good understanding of the tumorigenesis process and the mechanisms of developing chemotherapy resistance in cancer cells will help achieve significant advances in cancer treatment protocols. In recent years, there has been an increasing interest in long noncoding RNAs (lncRNAs). LncRNAs are no longer just a transcriptional noise, and many investigations proved their possible roles in regulating mandatory cellular functions. A lot of newly published studies confirmed the implication of lncRNAs in the tumor formation process and the multiple drug resistance in cancer chemotherapy. The main aim of this review is to focus on the lncRNAs' functions in the cell, their possible roles in the tumor formation process, and their roles in the development of chemotherapy resistance in different cancer cells.
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This report presents the synthesis and characterization of a range of benzimidazolium salts featuring 3-cyanopropyl groups on the 1st nitrogen atom and varied alkyl groups on the 3rd nitrogen atom within the benzimidazole structure. Benzimidazolium salts were synthesized by N-alkylation of 1-alkyl benzimidazole with 3-cyanopropyl-bromide. The new salts were characterized by 1 H and 13 C-NMR, FT-IR spectroscopic and elemental analysis techniques. In this study, the enzyme inhibition abilities of seven nitrile substituted benzimidazolium salts were investigated against acetylcholinesterase (AChE) and carbonic anhydrase isoenzymes I and II (hCA I and hCA II). They showed a highly potent inhibition effect on AChE, hCA I and hCA II (Ki values are in the range of 26.71-119.09â nM for AChE, 19.77 to 133.68â nM for hCA I and 13.09 to 266.38â nM for hCA II). Reflecting the binding mode of the synthesized cyanopropyl series, the importance of the 2,3,5,6-tetramethylbenzyl, 3-methylbenzyl and 3-benzyl groups for optimal interactions with target proteins, evaluated by molecular docking studies. At the same time, the docking findings support the inhibition constants (Ki ) values of the related compounds in this study. Potential compounds were also evaluated by their pharmacokinetic properties were predicted.
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Anhidrasas Carbónicas , Anhidrasas Carbónicas/metabolismo , Acetilcolinesterasa/metabolismo , Simulación del Acoplamiento Molecular , Sales (Química)/farmacología , Anhidrasa Carbónica II , Espectroscopía Infrarroja por Transformada de Fourier , Inhibidores de la Colinesterasa/química , Anhidrasa Carbónica I , Bencimidazoles , Nitrógeno , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/química , Relación Estructura-Actividad , Estructura MolecularRESUMEN
Aims: This paper aimed to investigate the antiviral drugs against Sars-Cov-2 main protease (MPro) using in silico methods. Material and Method: A search was made for antiviral drugs in the PubChem database and antiviral drugs such as Bictegravir, Emtricitabine, Entecavir, Lamivudine, Tenofovir, Favipiravir, Hydroxychloroquine, Lopinavir, Oseltamavir, Remdevisir, Ribavirin, Ritonavir were included in our study. The protein structure of Sars-Cov-2 Mpro (PDB ID: 6LU7) was taken from the Protein Data Bank (www.rcsb. Org) system and included in our study. Molecular docking was performed using AutoDock/Vina, a computational docking program. Protein-ligand interactions were performed with the AutoDock Vina program. 3D visualizations were made with the Discovery Studio 2020 program. N3 inhibitor method was used for our validation. Results: In the present study, bictegravir, remdevisir and lopinavir compounds in the Sars-Cov-2 Mpro structure showed higher binding affinity compared to the antiviral compounds N3 inhibitor, according to our molecular insertion results. However, the favipiravir, emtricitabine and lamuvidune compounds were detected very low binding affinity. Other antiviral compounds were found close binding affinity with the N3 inhibitor. Conclusion: Bictegravir, remdevisir and lopinavir drugs showed very good results compared to the N3 inhibitor. Therefore, they could be inhibitory in the Sars Cov-2 Mpro target.
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Antivirales , COVID-19 , Humanos , Antivirales/farmacología , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Lopinavir/farmacología , EmtricitabinaRESUMEN
Bacteria can form biofilms on any surface, which causes biofilm-associated infections and bacterial resistance to antibiotics. Thus, it is important to design new-generation non-chemotherapeutic nanoagents for effective antibacterial and antibiofilm strategies. Herein, the effects of the anchoring groups, which are imidazole and carboxylic acid, of zinc phthalocyanines (ZnPcs) sensitized TiO2 on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were investigated under light-emitting diode (LED) irradiation. The photocatalytic antibacterial activities of ZnPc-1/TiO2 and ZnPc-2/TiO2 on the bacterial strains were examined by monitoring the optical density value at 600 nm (OD600 nm). Glutathione (GSH) oxidation assay was used to measure the reactive oxygen species (ROS) generation activity of the compounds. Bacterial damages were imaged by scanning electron microscopy (SEM). According to our photocatalytic antibacterial mechanism, photogenerated electrons are transferred from Pcs to TiO2 and then react with O2, thus creating ROS, which causes damage to bacterial membrane, protein and biofilm destruction as well. Further, computational simulation analysis was used to show the interaction patterns of ZnPc-1 and ZnPc-2 with penicillin binding protein 2a (PBP2a) of S. aureus and FimH lectin protein (PDB:4XO8) of E. coli to elucidate the dark molecular antibacterial mechanism of the compounds. The obtained results from computational studies showed that ZnPc-2 binds firmly through bonds with the 1MWT protein from S. aureus. On the other hand, ZnPc-1 binds firmly through bonds with the 4XO8 protein from E. coli. From combining experimental and computational results, we can conclude that this strategy can be applied to different types of bacterial infections.
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Escherichia coli , Staphylococcus aureus , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , BiopelículasRESUMEN
Diabetes mellitus (DM) is still one of the most common diseases worldwide, and its prevalence is still increasing globally. According to the American and European recommendations, metformin is considered a first-line oral hypo-glycemic drug for controlling type 2 DM (T2DM) patients. Metformin is the ninth most often prescribed drug in the world, and at least 120 million diabetic people are estimated to receive the drug. In the last 20 years, there has been increasing evidence of vitamin B12 deficiency among metformin-treated diabetic patients. Many studies have reported that vitamin B12 deficiency is related to the ma-labsorption of vitamin B12 among metformin-treated T2DM patients. Vitamin B12 deficiency may have a very bad complication for the T2DM patient. In this review, we will focus on the effect of metformin on the absorption of vitamin B12 and on its proposed mechanisms in hindering vitamin B12 absorption. In addition, the review will describe the clinical outcomes of vitamin B12 deficiency in metformin-treated T2DM.
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Bioactive compounds found in plants also have pharmacological antiviral effects. Berberine (BBR), an alkaloid found naturally in plants, is one of the phytochemicals with a wide range of biological activities, including antiviral, anticancer, anti-inflammatory and anti-inflammatory. In this study, we firstly aimed to predict pIC50 values for selcted compounds and then extract the binding patterns of berberine and its derivatives in the Sars Cov-2 Master Protease structure via employing molecular docking approache. Our results showed that berberine and its derivatives have good binding affinities towared Sars Cov2 main protease protein. Based on docking results the pharamaccokinetic studies for berberine, berberrubine, demethylen-berberine, jatrorrhizin, and thalifendine, were conducted and showed a good pharamacokinetic properties as an oral drugs. For deep inspection, we utiilized molecular dynmaics simulation to examine the Sars Cov2 main protease-ligand stabilities. The molecular dynamics simulation and PCA investigations revealed that thalifendine have a strong willing to act as good bindinder to SARS-CoV-2 protease. Further, the network based pharamacology showed that these drugs mediate different pathways such as human T-cell leukemia virus 1 infection, viral carcinogenesis, human immunodeficiency virus 1 infection, kaposi sarcoma-associated herpesvirus infection and epstein-Barr virus infection.The findings of this study have an important recomendation for thalifendine for more in vivo and in vitro studies to work.Communicated by Ramaswamy H. Sarma.
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Berberina , COVID-19 , Infecciones por Virus de Epstein-Barr , Humanos , Berberina/farmacología , Simulación del Acoplamiento Molecular , Protoporfirinógeno-Oxidasa , Herpesvirus Humano 4 , SARS-CoV-2 , Aprendizaje Automático , Péptido Hidrolasas , Antiinflamatorios , Antivirales/farmacología , Simulación de Dinámica Molecular , Inhibidores de Proteasas/farmacologíaRESUMEN
In recent studies, it has been reported that ion channels play an important role in cancer formation. Therefore, it is possible that the use of pharmacological agents targeting ion channels will allow the development of new strategies for cancer treatment. In this study, we investigate the effect of imipramine on Eag1 channel expression in DU145 prostate cancer cells. Culture cells were divided into 4 groups as the control, 10, 50 and 75 µM imipramine. Eag1 channel currents and conductivity were determined by whole-cell patch-clamp technique and gene expression by real time-polymerase chain reaction (RT-PCR). Current records were taken before (at 0th minute, as control) and 10 min after imipramine administration to the cells. It was observed that all three doses of imipramine significantly reduced Eag1 currents and conductivity compared with the control. However, the differences between dose groups were not significant. Similarly, Eag1 channel protein expression was found to be significantly reduced for all three doses of imipramine compared with the control group, but there was no significant difference in gene expression between dose groups. Obtained results suggested that imipramine has the potential to be used as a pharmacological agent targeting the Eag1 channel in the treatment of prostate cancer.
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Imipramina , Neoplasias de la Próstata , Línea Celular Tumoral , Éter , Canales de Potasio Éter-A-Go-Go/genética , Humanos , Imipramina/farmacología , Masculino , Neoplasias de la Próstata/tratamiento farmacológicoRESUMEN
INTRODUCTION: Catalase (CAT), an antioxidant enzyme, catalyzes conversion of hydrogen peroxide to water and molecular oxygen, protecting cells against oxidative stress. The aim of this study was to investigate the possible association between CAT C262T polymorphism in the promoter region of the CAT gene and leukemia risk and to determine the relationship between CAT genotypes and CAT enzyme activities. MATERIAL AND METHODS: Genotypes of 102 cases and 112 healthy controls' genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism methods. Catalase activity was measured with the method of Aebi. RESULTS: The frequencies of the T allele among the cases and controls were 28.4% and 25.9%, respectively (p = 0.75). The frequencies of CC, CT, and TT among cases were 57.8%, 27.4%, and 14.7%, respectively, while in controls, the frequencies of CC, CT, and TT were 54.4%, 39.3%, and 6.3%, respectively, which were not significantly different. Although CAT enzyme activity was lower in leukemia patients with TT genotypes than in controls, this did not reach statistical significance (p = 0.37). CONCLUSIONS: This is the first report showing that CAT C262T polymorphism is not a genetic predisposing factor for the risk of leukemia in the Turkish population. However, additional research is needed to confirm these findings.
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OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a heterogeneous, highly heritable, a common childhood neurobehavioural disorder resulting from complex gene-gene and gene-environment interactions. The erythropoietin (Epo)/erythropoietin receptors (EpoR) system turned out to have additional important functions in nonhematopoietic tissue. In this study, we aimed to investigate the levels of Epo and and EpoR, and also their diagnostic values in children with ADHD. METHODS: A total of 70 children were included in the study, 35 drug-naive patients with ADHD (age: 6-12 years; male/female: 20/15) and 35 healthy controls (age: 6-12 years; male/female: 22/13). Serum Epo and EpoR levels was determined using a commercial sandwich enzyme-linked immunosorbent assay kit. RESULTS: The results indicated that the levels of Epo decreased in patients with ADHD compared to control (p < 0.05). On the other hand, EpoR levels increased in these patients (p < 0.05). Furthermore, the ratio of Epo/EpoR was significantly lower in ADHD patients than controls (p < 0.05). Receiver operator characteristic curve analysis showed high diagnostic performance for Epo and EpoR, areas under curve were 0.980 and 1.000, respectively. CONCLUSION: This is the first report to investigate the association between serum Epo and EpoR levels in ADHD patients. Our results indicated that Epo may play a role in the etiology of ADHD, and Epo therapy may be beneficial in these disorders if given in addition to the routine treatment of children with ADHD. Furthermore, our results reveal possible diagnostic value of Epo and EpoR.
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Aim: Major side effects of cyclophosphamide administration are immunosuppression and myelosuppression. The immunomodulatory effects of plant bioactive compounds on chemotherapy drug-induced immunosuppression may have significant effects in cancer treatment. For this reason, we investigated the immunomodulatory effect of myricetin, apigenin, and hesperidin in cyclophosphamide-induced immunosuppression in rats.Methods: In our study, a total of 64 rats were used, and divided into eight equal groups. These groups were: control, cyclophosphamide, cyclophosphamide + myricetin (100 mg/kg), cyclophosphamide + myricetin (200 mg/kg), cyclophosphamide + apigenin (100 mg/kg), cyclophosphamide + apigenin (200 mg/kg), cyclophosphamide + hesperidin (100 mg/kg), and cyclophosphamide + hesperidin (200 mg/kg). Myricetin, apigenin, and hesperidin pretreatments were performed for 14 d, while cyclophosphamide application (200 mg/kg) was performed only on the 4th day of the study. Levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, and natural killer cell cytotoxicity were determined. In addition, we measured pro-inflammatory cytokines, and followed lipid peroxidation and antioxidant markers and examined the histology of bone marrow, liver and spleen in all groups.Results: During cyclophosphamide treatment, all three phytochemicals increased the levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, antioxidant markers, and natural killer cell cytotoxicity. Moreover, the agents decreased the levels of pro-inflammatory cytokines and mediators, reduced lipid peroxidation markers, and reduced tissue damage in liver, spleen, and bone marrow.Conclusion: Our study demonstrated that myricetin, apigenin, and hesperidin can reduce the immunosuppressive effect of cyclophosphamide by enhancing both innate and adaptive immune responses, and these compounds may be useful immunomodulatory agents during cancer chemotherapy.
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Apigenina/farmacología , Ciclofosfamida/efectos adversos , Flavonoides/farmacología , Hesperidina/farmacología , Tolerancia Inmunológica/efectos de los fármacos , Animales , Ciclofosfamida/farmacología , Masculino , Ratas , Ratas WistarRESUMEN
PURPOSE: Rapid development in mobile phone technologies increase the average mobile phone usage duration. This increase also triggers exposure to radiofrequency radiation (RF), which is a risk factor for the health. In this study, it was aimed to investigate the effect of mobile phone working with LTE-Advanced Pro (4.5 G) mobile network on the optic nerve, which is responsible for the transmission of visual information. MATERIAL AND METHODS: Thirty-two rats divided into two groups as control (no RF, sham exposure) and experimental (RF exposure using a mobile phone with LTE-Advanced Pro network; 2 hours/day, 6 weeks). The visual evoked potential (VEP) was recorded and determined amplitudes and latencies of VEP waves. Optic nerve malondialdehyde level, catalase and superoxide dismutase activities were determined. Furthermore, ultrastructural and morphometric changes of optic nerve were evaluated. RESULTS: In VEP recordings, the mean VEP amplitudes of experimental group were significantly lower than control group. In ultrastructural evaluation, myelinated nerve fibres and glial cells were observed in normal histologic appearance both in sham and experimental group. However, by performing morphometric analysis, in the experimental group, axonal diameter and myelin thickness were shown to be lower and the G-ratio was higher than in the sham group. In the experimental group, malondialdehyde level was significantly higher and superoxide dismutase and catalase activities were significantly lower than sham group. There was a high correlation between VEP wave amplitudes and oxidative stress markers. CONCLUSION: Findings obtained in this study support optic nerve damage. These results point out an important risk that may decrease the quality of life.
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Teléfono Celular , Traumatismos del Nervio Óptico/etiología , Nervio Óptico/efectos de la radiación , Ondas de Radio/efectos adversos , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta en la Radiación , Potenciales Evocados Visuales/efectos de la radiación , Humanos , Masculino , Nervio Óptico/patología , Traumatismos del Nervio Óptico/patología , Estrés Oxidativo/efectos de la radiación , RatasRESUMEN
BACKGROUND: Diabetes mellitus (DM) has become more and more common and has a high morbidity and mortality rate worldwide. It is a multifactorial chronic disease affected by both genetic and environmental factors. OBJECTIVES: To evaluate the association between antioxidant enzyme activities and their genetic variations and the level of malondialdehyde (MDA) in type II diabetes patients living in the Adiyaman province in the southeast part of Turkey. MATERIAL AND METHODS: One hundred patients diagnosed with type II DM (T2DM) and 100 healthy controls were included in the study. Malondialdehyde levels and antioxidant enzyme activities were measured spectrophometrically. DNA isolation was performed and genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Our results revealed no significant differences in genotype distributions and allele frequencies of all polymorphisms between groups (p > 0.05). Significantly elevated MDA levels and a significant reduction in catalase (CAT) and paraoxonase (PON) enzyme activities were observed in patients compared to the control group in terms of study groups and genetic variations (p < 0.05). Moreover, CAT activity was reduced in TT genotype in terms of CAT -262 C/T polymorphism in patients (p < 0.05). Paraoxonase activity was observed to be lower in MM genotype in both groups (p < 0.05). CONCLUSIONS: CAT -262 C/T polymorphism may be one of the factors that lead to severe clinical situation in DM. Our results suggest that TT genotype may be more prone to lipid peroxidation.
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Diabetes Mellitus Tipo 2 , Polimorfismo Genético , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/genética , Frecuencia de los Genes , Genotipo , Humanos , TurquíaRESUMEN
Objectives Rheum ribes L. is a perennial plant that belongs to the family of Polygonaceae, which is often used in traditional therapy because it possesses many bioactivities, such as antioxidant and antibacterial ones. Here we examined the effect of different R. ribes L. extracts on oxidative stress in experimental diabetic rats. Methods Thirty-six rats were divided into six groups as follows: group I, control group; group II, diabetic rats; group III, diabetic rats treated with the aqueous extract of R. ribes L. by gavage at 50 mg/kg for 15 days; group IV, diabetic rats treated by gavage with the ethanolic extract of R. ribes L. at 50 mg/kg for 15 days; group V, nondiabetic rats treated by gavage with the aqueous extract of R. ribes L. at 50 mg/kg for 15 days; group VI, nondiabetic rats treated by gavage with the ethanol extract of R. ribes L. at 50 mg/kg for 15 days. After 15 days, the animals were sacrificed and the liver and kidney tissues of each animal were isolated. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) activities in the tissue samples were measured, and histopathologic examination was carried out. Results R. ribes L. was effective in reducing the oxidative stress and increasing the levels of the antioxidant enzymes. Increased levels of MDA and decreased levels of SOD, CAT and GSH-Px were observed in both the liver and kidney tissues in group II. Decreased levels of MDA and increased levels of SOD, CAT and GSH-Px were observed in group III compared with group II. In group IV, decreased levels of MDA and increased levels of SOD, CAT and GSH-Px were observed in comparison with group II. Conclusions Diabetes increases oxidative stress and causes a decrease in antioxidant enzyme levels. Both aqueous and ethanolic extracts of R. ribes L. decrease oxidative stress activity and increase the levels of antioxidant enzymes. The ethanol extract of R. ribes L. has a higher antioxidant effect than the aqueous extract.
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Nitric oxide is known as relaxing factor because it acts as a vasodilator, increases blood flow, and inhibits platelet aggregation and adhesion, on the other hand nitric oxide can modulate cellular and physiological processes to limit oxidative injury, limiting processes such as leukocyte adhesion. As the complete mechanism of myricetin and its cardiovascular benefits is not completely understood, the aim of this study was to investigate the antihypertensive activity of myricetin in human umbilical vein endothelial cell (HUVEC). Angiotensin converting enzyme (ACE) activity, nitric oxide production, reactive oxygen species (ROS) scavenger activity, cellular calcium concentration, and endothelial nitric oxide synthase (eNOS) activity and protein expression was investigated in HUVEC treated with different concentration of myricetin (1-60 µM). Myricetin increased nitric oxide production in HUVEC through decreased ROS levels and increased nitric oxide production and eNOS activation. Activation of eNOS enzyme was achieved by an increase of cellular calcium concentration. At the same examined concentration of myricetin, the activity of ACE was significantly inhibited. These findings indicate that myricetin may be helpful for lowering blood pressure; this could be achieved through dietary intervention or by the production of new antihypertensive treatments from a natural product.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Flavonoides/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Óxido Nítrico/biosíntesis , Células Cultivadas , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III , Peptidil-Dipeptidasa A/metabolismoRESUMEN
Purpose: Although radiotherapy (RT) is an important component of cancer treatment, it induces adverse tissue reactions in the around of cancer tissue. Therefore, radioprotectives are needed to protect normal tissues. The aim of this study was to investigate the radioprotective effect of N-acetylcysteine (NAC) on RT-induced cardiac damage in rats for the acute term.Materials and methods: The animals were divided into four groups. The rats in control group were injected with saline for 7 d; the rats in NAC group were injected NAC at dose of 240 mg/kg d for 7 d; the rats in RT group were injected with saline for 7 d plus was irradiated 1 h after the last injection and the rats in NAC + RT group were injected with NAC for 7 d and irradiated 1 h after the last NAC dose. The electrocardiogram was recorded and evaluated PR interval, QRS duration, QT interval, T wave alterations and heart rate. Serum interleukin-4, interleukin-6, tumor necrosis factor-alpha, interleukin 1 beta, galectin-3 levels and creatine kinase and creatine kinase isoenzyme-MB activities were determined in all groups. Also, tissue malondialdehyde (MDA) and nitric oxide levels, superoxide dismutase, catalase and glutathione peroxidase activities were determined. In addition, histological changes of heart were evaluated. All measurements were performed 24 h after RT.Results: In the RT group, findings supporting cardiac injury were observed in the electrocardiogram. Also, cytokine levels and oxidative stress were significantly increased. Pretreatment of rats with NAC ameliorated cardiac injury induced by RT.Conclusions: Our findings suggested that NAC may be a potential radioprotector which is capable of preventing cardiac damage.
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Acetilcisteína/farmacología , Corazón/efectos de la radiación , Protectores contra Radiación/farmacología , Animales , Citocinas/análisis , Electrocardiografía/efectos de la radiación , Femenino , Miocardio/metabolismo , Miocardio/patología , Estrés Oxidativo/efectos de los fármacos , Radioterapia/efectos adversos , Ratas , Ratas WistarRESUMEN
OBJECTIVES: The aim of this study was to assess the influence of plasminogen activator inhibitor-1 (PAI-1) 4G/5G or tissue plasminogen activator (tPA) I/D polymorphisms in chronic obstructive pulmonary disease (COPD) cases in a sample of Turkish population. METHODS: PAI-1 4G/5G and tPA Alu-repeat I/D genetic polymorphisms in 153 COPD subjects and 160 controls were investigated using PCR-RFLP and PCR methods, respectively. RESULTS: 4G allele frequency was 0.62 and 0.39 for COPD and control groups, respectively. 4G allele had an estimated 2.56- fold [95% CI = 1.85-3.53] increased risk of COPD. tPA I allele frequency was 0.55 and 0.50, for COPD and control groups, respectively. I allele had an estimated 1.19-fold [95% CI = 0.87-1.62] increased risk of COPD. CONCLUSIONS: PAI-1 4G/4G and 4G/5G genotypes seemed to play a key role in the pathophysiology of COPD in Turkish individuals.
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Enfermedad Pulmonar Obstructiva Crónica , Activador de Tejido Plasminógeno , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo Genético , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/genéticaRESUMEN
Prostate cancer is the most common cancer and leading cause of cancer death for males. Imipramine (IMI), which is a tricyclic antidepressant, has also been shown to has antineoplastic effect. This study was performed to investigate the radiosensitizing effect of IMI on DU145 prostate cancer cell. Cells were divided into 4 groups. Cell index, apoptotic activity, cell cycle arrest, oxidative stress and EAG1 channel currents were determined in all groups. Our findings showed that combined treatment with IMI and radiotherapy (RAD) did not enhance radiosensitivity of DU145 cells but as unexpected finding, treatment of IMI alone was more effective in DU145 cells.
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Canales de Potasio Éter-A-Go-Go/metabolismo , Imipramina/farmacología , Neoplasias de la Próstata/metabolismo , Fármacos Sensibilizantes a Radiaciones/farmacología , Ciclo Celular/efectos de los fármacos , Ciclo Celular/efectos de la radiación , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Neoplasias de la Próstata/terapia , RadioterapiaRESUMEN
Background: Fungicides describe all chemicals used to control fungi that infect plants. Luna Experience SC-400 is a new line of fungicide that consist of Fluopyram and Tebuconazole. Objective: In this study, We investigated the genotoxicty and cytotoxicty of Luna Experience-SC 400 using comet assay, micronucleus test and polychromatic erythrocytes number in rat bone marrow. The present study is the first report indicating the effects of genotoxic and cytotoxic of Luna experience SC-400 on rat bone marrow cells. Material and Methods: We used three different doses (5mg/kg, 10mg/kg, 20mg/kg) of Luna Experience SC 400 at 48 h intervals during 30 days by gavage in rats.Genotoxicity was evaluated using comet assay and micronucleus test and cytotoxicity was measured the PCE/NCE rate in rat bone marrow. Results: Based on these experimental results, we report that Luna Experience-SC 400 fungicide presents genotoxic and cytotoxic potential on rat bone marrow. There is a significant difference between negative control group and all the doses of Luna Experience-SC 400 (p < 0.05) for comet assay and micronucleus. Even moderate and high doses of fungicides seem to have reached the values of almost positive control group for Genetic Damage Index (GDI) and Damaged Cell Percentage (DCP). In this study, we also investigated the PCE/NCE rate. Fungicide caused a decrease in the level of significant in the PCE/NCE ratio (p < 0.05). Conclusion: Our in vivo study suggests that the gavage exposure to Luna experience SC 400 used in the present investigation may be genotoxic and cytotoxic in rat bone marrow in view of these findings. Because this findings is first report represented in the pesticide biology, it is important to carry out more investigations using various cytogenetic tests under different experimental conditions to definitively resolve the the possible genotoxic and cytotoxic risk associated with new generation pesticides-fungicides.
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Benzamidas/toxicidad , Médula Ósea/efectos de los fármacos , Fungicidas Industriales/toxicidad , Piridinas/toxicidad , Triazoles/toxicidad , Animales , Ensayo Cometa , Citotoxinas/farmacología , Relación Dosis-Respuesta a Droga , Pruebas de Micronúcleos , Mutágenos/farmacología , RatasRESUMEN
The nervous system is an important target of radiofrequency (RF) radiation exposure since it is the excitable component that is potentially able to interact with electromagnetic fields. The present study was designed to investigate the effects of 1,800 MHz RF radiation and the protective role of paricalcitol on the rat sciatic nerve. Rats were divided into four groups as control, paricalcitol, RF, and RF + paricalcitol. In RF groups, the rats were exposed to 1,800 MHz RF for 1 h per day for 4 weeks. Control and paricalcitol rats were kept under the same conditions without RF application. In paricalcitol groups, the rats were given 0.2 µg/kg/day paricalcitol, three times per week for 4 weeks. Amplitude and latency of nerve compound action potentials, catalase activities, malondialdehyde (MDA) levels, and ultrastructural changes of sciatic nerve were evaluated. In the RF group, a significant reduction in amplitude, prolongation in latency, an increase in the MDA level, and an increase in catalase activity and degeneration in the myelinated nerve fibers were observed. The electrophysiological and histological findings were consistent with neuropathy, and the neuropathic changes were partially ameliorated with paricalcitol administration. Bioelectromagnetics. 39:631-643, 2018. © 2018 Wiley Periodicals, Inc.