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1.
Medicine (Baltimore) ; 99(38): e21960, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957313

RESUMO

INTRODUCTION: Sperm DNA integrity has been considered as one of the important determinants of normal fertilization and embryonic development in natural and assisted pregnancy. It is difficult for men with high levels of sperm DNA fragmentation (SDF) in semen to conceive their partners naturally and assist in conception. The studies have found that the level of SDF in the semen of patients with varicocele (VC) was on the high side. In recent years, the effect of VC surgery on DNA fragmentation index has attracted the attention of researchers. In this study, we will evaluate the effectiveness of VC repair as a way to alleviate SDF and improve male fertility. METHODS AND ANALYSIS: Electronic databases including English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be searched from their inception to December 2020 to recognize related studies. All the randomized controlled trials of microsurgical varicocelectomy for the management of VC patients will be included. The potential outcome will include improvement in SDF, oxidative stress markers (reactive oxygen species, nitric oxide, and lipid peroxidation products), sperm chromatin compaction, other advanced sperm function characteristics, follow-up of fertility results. We will conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on April 5th of 2021. CONCLUSION: This systematic review will provide more evidence to assess whether varicocelectomy is an effective intervention for patients with SDF. The results will be published in a public issue journal and offer the urologists help to make clinical decisions. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published research. Since this research does not involve patients, personal privacy will not be affected. The results of this review will be distributed to peer-reviewed journals or submitted to relevant conferences. PROTOCOL REGISTRATION NUMBER: INPLASY202070119.


Assuntos
Fragmentação do DNA , Espermatozoides/patologia , Varicocele/cirurgia , Cromatina/metabolismo , Humanos , Masculino , Estresse Oxidativo/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
2.
Anticancer Res ; 40(9): 5035-5041, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32878791

RESUMO

BACKGROUND/AIM: Based on the cytotoxic agent (-)-zampanolide, N,N'-(arylmethylene)bisamides were designed and synthesized as candidate anti-cancer agents. Among them, N,N'-[(3,4-dimethoxyphenyl)methylene]biscinnamide (DPMBC) was identified as the most potent cytotoxic analog against cancer cells. In this study, we investigated the mechanisms underlying DPMBC-induced cell death in HL-60 human promyelocytic leukemia and PC-3 human prostate cancer cells. MATERIALS AND METHODS: Cell growth was assessed by the WST-8 assay. Induction of apoptosis was assessed by nuclear morphology, DNA ladder formation, and flow cytometry using Annexin V staining. Activation of factors in the apoptotic signaling pathway was assessed by western blot analyses. Knockdown of death receptor 5 (DR5) was performed using siRNA. RESULTS: DPMBC up-regulated expression levels of DR5 protein and induced apoptosis through the extrinsic apoptotic pathway mediated by DR5 and caspases. CONCLUSION: DPMBC is an extrinsic apoptosis inducer, which has potential as a therapeutic agent for cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Macrolídeos/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Antineoplásicos/química , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA , Relação Dose-Resposta a Droga , Humanos , Macrolídeos/química , Estrutura Molecular , RNA Interferente Pequeno/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
4.
PLoS One ; 15(7): e0236366, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702062

RESUMO

Deep sequencing of T-cell receptor (TCR) genes is powerful at profiling immune repertoire. To prepare a TCR sequencing library, multiplex polymerase chain reaction (mPCR) is widely applied and is highly efficient. That is, most mPCR products contain the region critical for antigen recognition, which also indicates regular V(D)J recombination. Multiplex PCR, however, may suffer from primer bias. A promising alternative is 5'-RACE, which avoids primer bias by applying only one primer pair. In 5'-RACE data, however, non-regular V(D)J recombination (e.g., TCR sequences without a V gene segment) has been observed and the frequency varies (30-80%) between studies. This suggests that the cause of or how to reduce non-regular TCR sequences is not yet well known by the science community. Although it is possible to speculate the cause by comparing the 5'-RACE protocols, careful experimental confirmation is needed and such a systematic study is still not available. Here, we examined the 5'-RACE protocol of a commercial kit and demonstrated how a modification increased the fraction of regular TCR-ß sequences to >85%. We also found a strong linear correlation between the fraction of short DNA fragments and the percentage of non-regular TCR-ß sequences, indicating that the presence of short DNA fragments in the library was the main cause of non-regular TCR-ß sequences. Therefore, thorough removal of short DNA fragments from a 5'-RACE library is the key to high data efficiency. We highly recommend conducting a fragment length analysis before sequencing, and the fraction of short DNA fragments can be used to estimate the percentage of non-regular TCR sequences. As deep sequencing of TCR genes is still relatively expensive, good quality control should be valuable.


Assuntos
Sequência de Aminoácidos/genética , DNA/genética , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/genética , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Sequência de Bases , Fragmentação do DNA , DNA Complementar/genética , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/imunologia , Humanos , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
6.
Int J Nanomedicine ; 15: 3471-3482, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547008

RESUMO

Introduction: Nanoparticles are at the forefront of rapidly developing nanotechnology and have gained much attention for their application as an effective drug delivery system and as a mediated therapeutic agent for cancer. However, the cytotoxicity of nanoparticles is still relatively unknown and, therefore, additional study is required in order to elucidate the potential toxicity of these nanoparticles on cells. Materials and Methods: Thus, the following work aimed to investigate the capability of Beta vulgaris (beetroot) water extract (BWE; 200 mg/kg) to protect hepatic tissue following silver nanoparticles (AgNPs; 80 mg/kg; >100 nm) intoxication in male rats. Results: AgNPs-intoxication elevated the liver function markers - including serum transaminases and alkaline phosphatase activities - and decreased serum levels of albumin and total proteins, in addition to disturbing the oxidation homeostasis. This is evidenced by the increased lipid peroxidation, the depleted glutathione, and the suppressed activity of superoxide dismutase and catalase. In addition, an apoptotic reaction was observed following AgNPs treatment, as indicated by the up-regulation of p53 and down-regulating Bcl-2 expressions, examined by the immunohistochemistry method. Furthermore, AgNPs exhibited a marked elevation in liver DNA damage that was indicated by an increase in tail length, tail DNA% and tail movement. However, BWE eliminated the biochemical and histological alterations, reflecting its hepatoprotection effect in response to AgNPs. Discussion: Collectively, the present data suggest that BWE could be used following AgNPs as a potential therapeutic intervention to minimize AgNPs-induced liver toxicity.


Assuntos
Beta vulgaris/química , Sucos de Frutas e Vegetais , Fígado/patologia , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Animais , Dano ao DNA , Fragmentação do DNA/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Testes de Função Hepática , Masculino , Nanopartículas Metálicas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/metabolismo
7.
Anticancer Res ; 40(5): 2525-2536, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366397

RESUMO

BACKGROUND/AIM: Mast cell transformation, as manifested in mastocytosis, can be a serious condition for which there are limited therapeutic options. Mastocytosis cells can be sensitive to histone deacetylase (HDAC) inhibitors, but their sensitivity to other histone-modifying enzymes has not been assessed. Here we addressed this issue. MATERIALS AND METHODS: Inhibitors of histone methyl transferases, histone demethylases, histone acetyl transferases and HDACs were tested for their effects on growth, viability, caspase-3 activation and annexin V/DRAQ7 staining in transformed mast cells. RESULTS: Transformed mast cells underwent cell death in response to histone methyl transferase and HDAC inhibition, but were not sensitive to histone demethylase or histone acetyl transferase inhibition. Histone methyl transferase inhibition led to cell death with characteristics of apoptosis, as judged by caspase-3 activation. However, DNA fragmentation was not apparent and Annexin V+/DRAQ7- cells were not predominant, suggesting a type of cell death differing from classical apoptosis. CONCLUSION: Histone methyl transferase inhibition could be developed as a novel regimen for targeting mastocytosis.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Histona Metiltransferases/antagonistas & inibidores , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Mastocitose/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Histonas/metabolismo , Humanos , Mastocitose/tratamento farmacológico , Mastocitose/etiologia , Mastocitose/patologia
8.
Clin Sci (Lond) ; 134(11): 1191-1218, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32432676

RESUMO

Myocardial infarction (MI) is the leading cause of mortality worldwide. Interleukin (IL)-33 (IL-33) is a cytokine present in most cardiac cells and is secreted on necrosis where it acts as a functional ligand for the ST2 receptor. Although IL-33/ST2 axis is protective against various forms of cardiovascular diseases, some studies suggest potential detrimental roles for IL-33 signaling. The aim of the present study was to examine the effect of IL-33 administration on cardiac function post-MI in mice. MI was induced by coronary artery ligation. Mice were treated with IL-33 (1 µg/day) or vehicle for 4 and 7 days. Functional and molecular changes of the left ventricle (LV) were assessed. Single cell suspensions were obtained from bone marrow, heart, spleen, and peripheral blood to assess the immune cells using flow cytometry at 1, 3, and 7 days post-MI in IL-33 or vehicle-treated animals. The results of the present study suggest that IL-33 is effective in activating a type 2 cytokine milieu in the damaged heart, consistent with reduced early inflammatory and pro-fibrotic response. However, IL-33 administration was associated with worsened cardiac function and adverse cardiac remodeling in the MI mouse model. IL-33 administration increased infarct size, LV hypertrophy, cardiomyocyte death, and overall mortality rate due to cardiac rupture. Moreover, IL-33-treated MI mice displayed a significant myocardial eosinophil infiltration at 7 days post-MI when compared with vehicle-treated MI mice. The present study reveals that although IL-33 administration is associated with a reparative phenotype following MI, it worsens cardiac remodeling and promotes heart failure.


Assuntos
Eosinófilos/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Interleucina-33/farmacologia , Infarto do Miocárdio/fisiopatologia , Sístole/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Citocinas/sangue , Fragmentação do DNA/efeitos dos fármacos , Diástole/efeitos dos fármacos , Eosinofilia/patologia , Eosinófilos/efeitos dos fármacos , Fibrose , Ventrículos do Coração/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/patologia , Mediadores da Inflamação/sangue , Interleucina-33/administração & dosagem , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Esplenomegalia/patologia , Regulação para Cima/efeitos dos fármacos , Remodelação Ventricular/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
9.
Toxicon ; 181: 57-68, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32353570

RESUMO

This study aimed to identify the bioactive compounds of the ethyl acetate extract of Aspergillus niger SH2-EGY using GC-MS and to evaluate their protective role against aflatoxin B1 (AFB1)-induced oxidative stress, genotoxicity and cytotoxicity in rats. Six groups of male Sprague-Dawley rats were treated orally for 4 weeks included the control group, AFB1-treated group (80 µg/kg b.w); fungal extract (FE)-treated groups at low (140) or high dose (280) mg/kg b.w and the groups treated with AFB1 plus FE at the two tested doses. The GC-MS analysis identified 26 compounds. The major compounds found were 1,2,3,4,6-Penta-trimethylsilyl Glucopyranose, Fmoc-L-3-(2-Naphthyl)-alanine, D-(-)-Fructopyranose, pentakis (trimethylsilyl) ether, bis (2-ethylhexyl) phthalate, trimethylsilyl ether-glucitol, and octadecanamide, N-(2- methylpropyl)-N-nitroso. The in vivo results showed that AFB1 significantly increased serum ALT, AST, creatinine, uric acid, urea, cholesterol, triglycerides, LDL, carcinoembryonic antigen, alpha-fetoprotein, interleukin-6, Malondialdehyde, nitric oxide, Bax, caspase-3 and P53 mRNA expression, chromosomal aberrations and DNA fragmentation. It decreased serum TP, albumin, HDL, Bcl-2 mRNA expression, hepatic and renal TAC, SOD and GPx content and induced histological changes in the liver and kidney. FE prevented these disturbances in a dosage-dependent manner. It could be concluded that A. niger SH2-EGY extract is safe a promising agent for pharmaceutical and food industries.


Assuntos
Aflatoxina B1/toxicidade , Antioxidantes/uso terapêutico , Aspergillus niger , Animais , Fragmentação do DNA/efeitos dos fármacos , Inativação Metabólica/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
10.
Environ Sci Pollut Res Int ; 27(23): 28890-28898, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32415451

RESUMO

Agrochemicals are one the most significant sources of environmental pollution. Cytotoxicity and genotoxicity are the serious side effects of fungicide. In the current study, I have evaluated acute cytotoxicity and genotoxicity of triphenyltin (TPT) on human hepatic carcinoma (HepG2) cells and the ameliorating effect of ascorbic acid for 24 h. In this experiment, I have exposed HepG2 cells to ascorbic acids (50, 100, and 200 µM) simultaneously and 24 h prior triphenyltin (TPT, 400 ng/ml) exposure for 24 h to determine the protective effect of ascorbic acid by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and NRU (neutral red uptake) assays. Oxidative stress, such as intracellular reactive oxygen species and glutathione levels, was measured in HepG2 cells. The intracellular reactive oxygen species was evaluated using fluorescent probe DCFDA (6-carboxy-2',7' dichloro-dihydrofluorescein diacetate). Apoptosis and genotoxicity effects of TPT in HepG2 cells were determined using flow cytometry and comet assay. The result of these experiments showed that the TPT compound (400 ng/ml) induced cytotoxicity, oxidative stress and apoptosis, and DNA damage in HepG2 cells.Ascorbic acid reduced cytotoxicity, oxidative stress, apoptosis, and genotoxicity induced by TPT. Thus, ascorbic acid is a potent antioxidant, and it showed a significant protective effect against toxicity induced by TPT in HepG2 cells.


Assuntos
Ácido Ascórbico , Estresse Oxidativo , Sobrevivência Celular , Dano ao DNA , Fragmentação do DNA , Suplementos Nutricionais , Humanos , Fígado , Compostos Orgânicos de Estanho , Espécies Reativas de Oxigênio
11.
Life Sci ; 250: 117599, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32234491

RESUMO

Chemotherapeutic antibiotic doxorubicin belongs to the anthracycline class, slaughters not only the cancer cells but also non-cancerous cells even in the non-targeted organs thereby resulting in the toxicity. The liver is primarily involved in the process of detoxification and this mini-review we focused mainly to investigate the molecular mechanisms heading hepatotoxicity caused due to doxorubicin administration. The alterations in the doxorubicin treated liver tissue include vacuolation of hepatocytes, degeneration of hepatocyte cords, bile duct hyperplasia and focal necrosis. About the literature conducted, hepatotoxicity caused by doxorubicin has been explained by estimating the levels of liver serum biomarkers, ROS production, antioxidant enzymes, lipid peroxidation, and mitochondrial dysfunction. The liver serum biomarkers such as ALT and AST, elated levels of free radicals inducing oxidative stress characterized by a surge in Nrf-2, FOXO-1 and HO-1 genes and diminution of anti-oxidant activity characterized by a decline in SOD, GPx, and CAT genes. The augmented levels of SGOT, SGPT, LDH, creatine kinase, direct and total bilirubin levels also reveal the toxicity in the hepatic tissue due to doxorubicin treatment. The molecular insight of hepatotoxicity is mainly due to the production of ROS, ameliorated oxidative stress and inflammation, deteriorated mitochondrial production and functioning, and enhanced apoptosis. Certain substances such as extracts from medicinal plants, natural products, and chemical substances have been shown to produce an alleviating effect against the doxorubicin-induced hepatotoxicity are also discussed.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Doxorrubicina/efeitos adversos , Fígado/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose , Fragmentação do DNA , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Inflamação , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
12.
Urol Clin North Am ; 47(2): 147-155, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32272986

RESUMO

For men with obstructive azoospermia, several surgical sperm retrieval techniques can facilitate conception with assisted reproductive technology. The evolution of both percutaneous and open approaches to sperm retrieval has been affected by technological innovations, including the surgical microscope, in vitro fertilization, and intracytoplasmic sperm injection. Further modifications to these procedures are designed to minimize patient morbidity and increase the quality and quantity of sperm samples. Innovative technologies promise to further ameliorate outcomes by selecting the highest quality sperm. Although various approaches to surgical sperm retrieval are now well established, several advancements in sperm selection and optimization are being developed.


Assuntos
Azoospermia/diagnóstico , Azoospermia/genética , Fertilização In Vitro/métodos , Injeções de Esperma Intracitoplásmicas/métodos , Recuperação Espermática , Fragmentação do DNA , Humanos , Masculino , Análise do Sêmen
13.
Environ Toxicol ; 35(9): 930-941, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32309901

RESUMO

Platinum nanoparticles (PtNPs) attract much attention due to their excellent biocompatibility and catalytic properties, but their toxic effects on normal (CHANG) and cancerous (HuH-7) human liver cells are meagre. The cytotoxic and apoptotic effects of PtNPs (average size, 3 nm) were determined in CHANG and HuH-7 cells. After treating these cells were with PtNPs (10, 50, 100, 200, and 300 µg/mL) for 24 and 48 hours, we observed dose- and time-dependent cytotoxicity, as evaluated by using (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide, a tetrazole) (MTT) and neutral red uptake (NRU) assays. The production of reactive oxygen species (ROS) was increased in both cells after treatment with the above dose of PtNPs for 24 and 48 hours. Determination of morphological changes of cells, chromosome condensation, mitochondrial membrane potential, and caspase-3 assays showed that PtNPs induce cytotoxicity and apoptosis in CHANG and HuH-7 cells by altering the cell morphology and density, increasing cell population in apoptosis, and causing chromosome condensation. Furthermore, we have studied fragmentation of DNA using alkaline single cell gel electrophoresis and expression of apoptotic genes by real-time PCR (RT-PCR). The percentage of DNA fragmentation was more at 300 µg/mL for 48 hours in both cells, but slightly more fragmentation was found in HuH-7 relative to CHANG cells. Considering all of the above parameters, PtNPs elicited cytotoxicity on CHANG and HuH-7 cells by blocking cell proliferation and inducing apoptosis. Thus this study may be useful in in vitro laboratory studies using cell lines for screening the genotoxic and apoptotic potential of nanoparticles.


Assuntos
Apoptose/efeitos dos fármacos , Dano ao DNA , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacos , Platina/farmacologia , Apoptose/genética , Caspase 3/genética , Caspase 3/metabolismo , Morte Celular , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Humanos , Fígado/metabolismo , Fígado/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/genética , Platina/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
14.
Georgian Med News ; (299): 26-29, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32242839

RESUMO

According to the statistics of the Russian Federation, the number of patients with male infertility increased by 60.3% over the past 12 years. Objective - to evaluate the activity of peripheral blood leukocytes, the rate of their production of reactive oxygen species, and the DNA fragmentation index in men with non-obstructive azoospermia. To solve this problem, we examined 65 men with non-obstructive idiopathic azoospermia. A control group consisted of 20 healthy fertile men. All patients underwent examination of ejaculate with measurement of levels of reactive oxygen species (ROS) and DNA fragmentation. To identify additional links in the pathogenesis of infertility, we determined the functional activity of peripheral blood leukocytes by registering luminol-dependent chemiluminescence (LCH) of leukocytes. The functional activity of leukocytes in men with azoospermia was found to be 4.5 times higher than in healthy men (p<0.01). We found that with such leukocyte activity the level of ROS and DNA fragmentation was 6 times higher in patients with infertility compared to the control group.


Assuntos
Azoospermia , Fragmentação do DNA , Infertilidade Masculina/etiologia , Leucócitos/fisiologia , Espermatozoides/metabolismo , Humanos , Masculino , Espécies Reativas de Oxigênio , Federação Russa , Motilidade Espermática/fisiologia
15.
Environ Sci Pollut Res Int ; 27(18): 23188-23198, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32333355

RESUMO

A large number of plant extracts have demonstrated to provide health benefits and mitigate several disease conditions. However, at the molecular and cellular levels, few studies have been conducted. The present work was designed to study the effect of Myrtus communis leaf extract (ME) (300 mg/kg bw) against hepatotoxicity induced by monosodium glutamate (MSG) (100 mg/kg bw), and acrylamide (ACR) (20 mg/kg bw) in male rats and determining its molecular and cellular mechanisms. The data showed that the treatment with MSG and/or ACR induced significant changes in numerous biomarkers (Bcl-2 and the programmed cell death protein-1) related to liver damage, as recorded by genotoxicity, apoptosis, and histopathological changes. On the other side, the oral administration of ME (300 mg/kg bw) improved the hepatic conditions as confirmed by the improvement in cell viability, programmed cell death, and histopathological alterations. It can be concluded that the consumption of ME might be useful for minimizing the occurred hepatotoxicity through up-regulation of the key apoptotic regulators as well as the improvement of DNA content and cell cycle restoration. Graphical abstract.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Myrtus , Acrilamida , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Fragmentação do DNA , Masculino , Extratos Vegetais , Ratos , Glutamato de Sódio
16.
PLoS One ; 15(3): e0224052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32168344

RESUMO

BACKGROUND: Codeine, a 3-methylmorphine, and other related opioids have been implicated in androgen suppression, although the associated mechanisms remain unclear. AIM: Therefore, the objective of the current study was to elucidate the in vivo molecular mechanisms underlying codeine-induced androgen suppression. METHODS: This study made use of twenty-one healthy male rabbits, distributed into three groups randomly, control and codeine-treated groups. The control had 1ml of normal saline daily p.o. The codeine-treated groups received either 4mg/kg b.w of codeine or 10mg/kg b.w of codeine p.o. for six weeks. Reproductive hormonal profile, testicular weight, testicular enzymes, oxidative and inflammatory parameters, testicular DNA fragmentation, histological examination and apoptosis marker were evaluated to examine the effects of codeine use. KEY FINDINGS: Oral administration of codeine resulted in testicular atrophy and alterations in testicular histomorphology, elevated testicular enzymes, and suppression of circulatory and intra-testicular testosterone. These changes were associated with a marked rise in oxidative markers and decline in the activities of testicular enzymatic antioxidants, as well as oxidative DNA damage, inflammatory response, testicular DNA fragmentation, and caspase-dependent apoptosis (p<0.05). SIGNIFICANCE: In conclusion, chronic codeine use resulted in testicular degeneration and testosterone suppression, which is attributable to TNF-α/nitric oxide-/oxidative stress-mediated caspase-dependent apoptotic testicular cell death and loss of testicular function.


Assuntos
Caspase 3/metabolismo , Codeína/toxicidade , Fragmentação do DNA/efeitos dos fármacos , Óxido Nítrico/metabolismo , Testículo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Administração Oral , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Codeína/administração & dosagem , Masculino , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Testículo/metabolismo , Testosterona/metabolismo
17.
Toxicol Appl Pharmacol ; 393: 114942, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32142724

RESUMO

Implications of lead (Pb) exposure in dysregulated spermatogenesis in sexually active individuals during adulthood is well established; however, the effect of Pb exposure on spermatogenesis in the early stages of puberty is not clear yet. Moreover, the mechanism of Pb mediated dysregulation of spermatogenesis in adults is also poorly understood. Exposure to environmental toxicants during puberty may cause serious consequences in adulthood causing developmental retardations, especially in the reproductive system. Here we investigated the effects of lead exposure on spermatogenesis at the onset of puberty and the underlying mechanisms of these effects. Male ICR mice were exposed to low (50 mg/L) and high (200 mg/L) doses of Pb through the drinking water for 90 days. At the end of this period, the blood Pb level of the low-dose and high-dose exposure groups were found 6.14 ± 0.34 µg/dL and 11.92 ± 2.92 µg/dL respectively which were in agreement with the US CDC-recommended (5 µg/dL) and Chinese CDC-recommended (10 µg/dL) reference blood Pb level for the children. Although no visible toxicity was observed in either group, Pb exposure caused considerable histopathological changes in testis and epididymis; increased sperm DNA fragmentation indices as well as disrupted sperm heads and head-neck conjunctions. Moreover, both low and high-dose Pb exposures caused aberrant expressions of several important spermatogenesis-related genes in epididymis and testis. These results suggest that although the blood Pb levels are close to the recommended-reference values, low dose Pb exposure at the onset of puberty can disrupt spermatogenesis-related gene expression and cause abnormal mouse spermatogenesis.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Infertilidade Masculina/induzido quimicamente , Intoxicação por Chumbo/complicações , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Animais , Fragmentação do DNA , Água Potável , Epididimo/patologia , Infertilidade Masculina/patologia , Chumbo/sangue , Masculino , Camundongos , Camundongos Endogâmicos ICR , Maturidade Sexual , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/patologia
19.
Food Chem Toxicol ; 137: 111134, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32006631

RESUMO

Tebuconazole is an effective systemic fungicide that belongs to the triazoles family. It has been widely used in both agricultural and medical sectors for the control of fungal diseases. Although TEB poses serious threats to mammals health, studies regarding its cardiotoxicity are very limited. Thus, we aimed to evaluate the effects of TEB on some biochemical parameters, the induction of apoptosis and DNA damage in the heart tissue. Male Wistar rats were treated with TEB at varied oral doses for 28 consecutive days. This study demonstrates that TEB decreased cardiac acetylcholinesterase, increased serum marker enzymes such as creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH), and altered the lipid profile by increasing serum levels of total cholesterol (T-CHOL), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C) levels. Furthermore, TEB increased levels of p53 and Bax/Bcl2 ratio, released the cytochrome c into the cytosol and activated caspase-9 and caspase-3. Besides, our results showed that TEB induced genotoxic effects. TEB induced DNA fragmentation and increased the frequency of micronucleated bone marrow cells. Moreover, TEB treatment developed fibrosis in the myocardium. Our results suggest that TEB exposure may affect myocardial cells normal functioning and triggers apoptosis.


Assuntos
Cardiotoxicidade/etiologia , Fungicidas Industriais/toxicidade , Triazóis/toxicidade , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade/genética , Cardiotoxicidade/metabolismo , Cardiotoxicidade/fisiopatologia , LDL-Colesterol/metabolismo , Citocromos c/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Humanos , Masculino , Ratos , Ratos Wistar , Triglicerídeos/metabolismo
20.
Nat Methods ; 17(3): 319-327, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32042188

RESUMO

Mapping open chromatin regions has emerged as a widely used tool for identifying active regulatory elements in eukaryotes. However, existing approaches, limited by reliance on DNA fragmentation and short-read sequencing, cannot provide information about large-scale chromatin states or reveal coordination between the states of distal regulatory elements. We have developed a method for profiling the accessibility of individual chromatin fibers, a single-molecule long-read accessible chromatin mapping sequencing assay (SMAC-seq), enabling the simultaneous, high-resolution, single-molecule assessment of chromatin states at multikilobase length scales. Our strategy is based on combining the preferential methylation of open chromatin regions by DNA methyltransferases with low sequence specificity, in this case EcoGII, an N6-methyladenosine (m6A) methyltransferase, and the ability of nanopore sequencing to directly read DNA modifications. We demonstrate that aggregate SMAC-seq signals match bulk-level accessibility measurements, observe single-molecule nucleosome and transcription factor protection footprints, and quantify the correlation between chromatin states of distal genomic elements.


Assuntos
Cromatina/química , Fragmentação do DNA , Saccharomyces cerevisiae/química , Adenosina/análogos & derivados , Adenosina/química , Linhagem Celular , Imunoprecipitação da Cromatina , Ilhas de CpG , Metilação de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metilação , Metiltransferases/genética , Nucleossomos/química , Regiões Promotoras Genéticas , Ligação Proteica
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