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1.
Life Sci ; 295: 120423, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35196530

RESUMO

Hepatocyte growth factor (HGF) has been proved to protect the liver against α-naphthylisothiocyanate (ANIT)-induced cholestasis by acting as an antioxidant agent and redirecting toxic biliary solutes towards blood for urinary excretion. However, this may represent an additional potential risk for kidney integrity, which is already compromised by the cholestatic process itself (cholemic nephropathy). Therefore, in the present work, we studied the renal damage caused by ANIT-induced cholestasis and whether it is aggravated or, on the contrary, counteracted by HGF; if the latter holds, the involvement of its antioxidant properties will be ascertained. ANIT-induced cholestatic deleterious renal effects were corroborated by the presence of urine bile salts, impairment of renal function, and the alterations of renal damage markers, such as HSP72, creatinine clearance, and albuminuria. HGF fully reverted all these, and the cast formation in the tubules was significantly decreased. These findings were associated with the control of renal oxidative stress. In summary, despite HGF enhancing the overload of potentially harmful biliary constituents that the kidney should remove from the bloodstream as an alternative depuration organ in cholestasis, it simultaneously protects the kidney from this damage by counteracting the prooxidant effects resulting from this harmful exposure.


Assuntos
Colestase/tratamento farmacológico , Fator de Crescimento de Hepatócito/farmacologia , Nefropatias/fisiopatologia , 1-Naftilisotiocianato/efeitos adversos , 1-Naftilisotiocianato/farmacologia , Animais , Antioxidantes/farmacologia , Ácidos e Sais Biliares/metabolismo , Ductos Biliares/fisiopatologia , Colestase/sangue , Colestase/metabolismo , Modelos Animais de Doenças , Fator de Crescimento de Hepatócito/metabolismo , Rim/metabolismo , Nefropatias/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
2.
Cancers (Basel) ; 13(7)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917315

RESUMO

Non-alcoholic fatty liver disease (NAFLD) and progression to non-alcoholic steatohepatitis (NASH) result as a consequence of diverse conditions, mainly unbalanced diets. Particularly, high-fat and cholesterol content, as well as carbohydrates, such as those commonly ingested in Western countries, frequently drive adverse metabolic alterations in the liver and promote NAFLD development. Lipid liver overload is also one of the main risk factors for initiation and progression of hepatocellular carcinoma (HCC), but detailed knowledge on the relevance of high nutritional cholesterol remains elusive. We were aimed to characterize HCC development in mice fed with a Western diet (high in lipids and cholesterol) and to identify molecular alterations that define a subtype of liver cancer induced by lipid overload. Mice under western or high cholesterol diets more frequently developed tumors with a more aggressive phenotype than animals fed with a chow diet. Associated changes involved macrophage infiltration, angiogenesis, and stemness features. RNA-seq revealed a specific gene expression signature (Slc41a; Fabp5; Igdcc4 and Mthfd1l) resembling the adverse phenotypic features and poor clinical outcomes seen in patients with HCC. In conclusion; consumption of lipid enriched diets; particularly cholesterol; could accelerate HCC development with an aggressive phenotype and poor prognosis.

3.
J Clin Exp Dent ; 13(3): e318-e322, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33680335

RESUMO

Aspergillosis, aka fungal ball (FB), is classified as a type of non-invasive fungal rhinosinusitis, which usually occurs unilaterally in the maxillary sinus of an immunocompromised patient. Its diagnosis is complex and depends on the association between clinical, imaging, and histopathological exams. There are many treatments for fungal infections of the paranasal sinuses, so early diagnosis is extremely important to determine the appropriate treatment. This paper reports an unusual clinical case of aspergillosis present bilaterally inside the maxillary sinuses of a healthy patient, associated with mucous retention cysts, whose imaging exams and transnasal endoscopy were not sufficient to precisely identify the lesion. Its diagnosis and definitive treatment were obtained only after orthognathic surgery and integration between a multidisciplinary team. Key words:Aspergillosis, communicable diseases, fungal ball, infectious disease, orthognathic surgery.

4.
Ann Hepatol ; 25: 100339, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33675999

RESUMO

INTRODUCTION AND OBJECTIVES: It is well-known that signaling mediated by the hepatocyte growth factor (HGF) and its receptor c-Met in the liver is involved in the control of cellular redox status and oxidative stress, particularly through its ability to induce hepatoprotective gene expression by activating survival pathways in hepatocytes. It has been reported that HGF can regulate the expression of some members of the NADPH oxidase family in liver cells, particularly the catalytic subunits and p22phox. In the present work we were focused to characterize the mechanism of regulation of p22phox by HGF and its receptor c-Met in primary mouse hepatocytes as a key determinant for cellular redox regulation. MATERIALS AND METHODS: Primary mouse hepatocytes were treated with HGF (50 ng/mL) at different times. cyba expression (gene encoding p22phox) or protein content were addressed by real time RT-PCR, Western blot or immunofluorescence. Protein interactions were explored by immunoprecipitation and FRET analysis. RESULTS: Our results provided mechanistic information supporting the transcriptional repression of cyba induced by HGF in a mechanism dependent of NF-κB activity. We identified a post-translational regulation mechanism directed by p22phox degradation by proteasome 26S, and a second mechanism mediated by p22phox sequestration by c-Met in plasma membrane. CONCLUSION: Our data clearly show that HGF/c-Met exerts regulation of the NADPH oxidase by a wide-range of molecular mechanisms. NADPH oxidase-derived reactive oxygen species regulated by HGF/c-Met represents one of the main mechanisms of signal transduction elicited by this growth factor.


Assuntos
Grupo dos Citocromos b/fisiologia , Fator de Crescimento de Hepatócito/fisiologia , Hepatócitos/metabolismo , NADPH Oxidases/fisiologia , Proteínas Proto-Oncogênicas c-met/fisiologia , Transdução de Sinais/fisiologia , Animais , Técnicas de Cultura de Células , Hepatócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Biossíntese de Proteínas , Transcrição Gênica
5.
J Cell Physiol ; 236(5): 4076-4090, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33174245

RESUMO

Growth differentiation factor 11 (GDF11) has been characterized as a key regulator of differentiation in cells that retain stemness features. Recently, it has been reported that GDF11 exerts tumor-suppressive properties in hepatocellular carcinoma cells, decreasing clonogenicity, proliferation, spheroid formation, and cellular function, all associated with a decrement in stemness features, resulting in mesenchymal to epithelial transition and loss of aggressiveness. The aim of the present work was to investigate the mechanism associated with the tumor-suppressive properties displayed by GDF11 in liver cancer cells. Hepatocellular carcinoma-derived cell lines were exposed to GDF11 (50 ng/ml), RNA-seq analysis in Huh7 cell line revealed that GDF11 exerted profound transcriptomic impact, which involved regulation of cholesterol metabolic process, steroid metabolic process as well as key signaling pathways, resembling endoplasmic reticulum-related functions. Cholesterol and triglycerides determination in Huh7 and Hep3B cells treated with GDF11 exhibited a significant decrement in the content of these lipids. The mTOR signaling pathway was downregulated, and this was associated with a reduction in key proteins involved in the mevalonate pathway. In addition, real-time metabolism assessed by Seahorse technology showed abridged glycolysis as well as glycolytic capacity, closely related to an impaired oxygen consumption rate and decrement in adenosine triphosphate production. Finally, transmission electron microscopy revealed mitochondrial abnormalities, such as cristae disarrangement, consistent with metabolic changes. Results provide evidence that GDF11 impairs cancer cell metabolism targeting lipid homeostasis, glycolysis, and mitochondria function and morphology.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Carcinoma Hepatocelular/metabolismo , Fatores de Diferenciação de Crescimento/metabolismo , Lipogênese , Neoplasias Hepáticas/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Glicólise , Humanos , Neoplasias Hepáticas/patologia , Consumo de Oxigênio , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
6.
Vet Med Sci ; 7(1): 136-140, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810898

RESUMO

Traumatic reticuloperitonitis combined with embolic pneumonia and hepatitis is unusual signs of foreign body syndrome in cattle. A 4-year-old Holstein bull presented decreased appetite, dry cough, progressive weight loss, sternal recumbence and reluctance to stand and move. Laboratory tests revealed leucocytosis (18.4 × 103 /µl) accompanied by neutrophilia (10.48 × 103 /µl), and monocytosis (1.28 × 103 /µl), hyperglobulinaemia (6.3 g/dl), hypoalbuminaemia (1.5 g/dl), hyperfibrinogenaemia (10 g/L) and severe increase in gamma-glutamyl transferase activity (1,216 U/L). Reticular ultrasonographical examination showed a large amount of hyperechoic and hypoechoic content between the reticular serosa and the hepatic visceral surface. The main gross findings included fibrin deposition and adhesions between the reticulum, liver and diaphragm surfaces; a 4.0 mm in diameter transmural reticular perforation; a 12.0-cm diameter and scarce small randomly abscesses in the liver's parenchyma. The lungs presented multifocal areas of suppurative embolic foci (pulmonary abscesses), interstitial emphysema and multifocal fibrin deposition on the pleural surface. Ancillary diagnostic tests, such as ultrasonography and laboratory test, associated with clinical evaluation, may increase the accuracy of the correct diagnosis and avoid wasting time and money on untreatable cases.


Assuntos
Doenças dos Bovinos/diagnóstico , Corpos Estranhos/veterinária , Hepatite Animal/diagnóstico , Peritonite/veterinária , Pneumonia/veterinária , Animais , Bovinos , Doenças dos Bovinos/diagnóstico por imagem , Doenças dos Bovinos/etiologia , Corpos Estranhos/complicações , Hepatite Animal/diagnóstico por imagem , Hepatite Animal/etiologia , Masculino , Peritonite/diagnóstico , Peritonite/diagnóstico por imagem , Peritonite/etiologia , Pneumonia/diagnóstico , Pneumonia/diagnóstico por imagem , Pneumonia/etiologia
7.
Femina ; 49(1): 52-57, 2021. tab
Artigo em Português | LILACS | ID: biblio-1146936

RESUMO

O trabalho avalia o comportamento de risco para infecções sexualmente transmissíveis (ISTs) em estudantes do ensino médio de Urussanga-SC. A pesquisa foi observacional transversal, descritiva, com coleta de dados primários e abordagem quantitativa. A população estudada constou de alunos do ensino médio de escolas públicas e privadas de Urussanga-SC no ano de 2019. A amostra foi constituída por 178 indivíduos, sendo majoritariamente composta pelo sexo feminino (61,4%), e a média de idades foi de 16 anos (±1,04). Do total, 50% haviam iniciado as atividades sexuais. Entre o sexo feminino, 48,1% relataram um parceiro, contrapondo-se com o sexo masculino, no qual 40,7% relataram quatro ou mais. Em relação ao conhecimento sobre manifestações de ISTs, 62,4% informaram dor na região genital como sinal de alerta, todavia a presença de feridas e corrimento foi reconhecida por menos de 40% dos adolescentes. A maioria dos adolescentes já recebeu orientações sobre sexualidade e afirmou possuir conhecimento sobre ela, porém os resultados demonstram falha no entendimento, sendo evidente a importância da educação sexual nas escolas.(AU)


The assessed work examined risk behavior for sexually transmitted infections (STIs) in high school students from Urussanga-SC. A cross-sectional, descriptive observational study, using primary data collection and a quantitative approach. The population studied contained high school students from public and private schools in Urussanga- SC in 2019. The sample was mainly composed of females and the average age was 16 years. From the total, 50% already started sexual activities. Of the female sex, 48.1% refer to one partner, by contrast, 40,7% of the male sex, refer to four or more partners. Regarding manifestations, 62.4% reported pain in the genital region as a warning sign, however, the presence of wounds and discharge was registered by less than 40% of adolescents. Most adolescents have already received some guidance on sexuality and reported having knowledge about the subject. Nevertheless, the results presented a lack of understanding, highlighting the importance of sex education in schools.(AU)


Assuntos
Humanos , Masculino , Feminino , Gravidez , Adolescente , Infecções Sexualmente Transmissíveis/prevenção & controle , Comportamento do Adolescente , Saúde do Adolescente , Saúde Sexual , Gravidez na Adolescência/prevenção & controle , Brasil/epidemiologia , Estudos Transversais
8.
Biochem Pharmacol ; 174: 113812, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31954718

RESUMO

Cholestasis is a clinical syndrome common to a large number of hepatopathies, in which either bile production or its transit through the biliary tract is impaired due to functional or obstructive causes; the consequent intracellular retention of toxic biliary constituents generates parenchyma damage, largely via oxidative stress-mediated mechanisms. Hepatocyte growth factor (HGF) and its receptor c-Met represent one of the main systems for liver repair damage and defense against hepatotoxic factors, leading to an antioxidant and repair response. In this study, we evaluated the capability of HGF to counteract the damage caused by the model cholestatic agent, α-naphthyl isothiocyanate (ANIT). HGF had clear anti-cholestatic effects, as apparent from the improvement in both bile flow and liver function test. Histology examination revealed a significant reduction of injured areas. HGF also preserved the tight-junctional structure. These anticholestatic effects were associated with the induction of basolateral efflux ABC transporters, which facilitates extrusion of toxic biliary compounds and its further alternative depuration via urine. The biliary epithelium seems to have been also preserved, as suggested by normalization in serum GGT levels, CFTR expression and cholangyocyte primary cilium structure our results clearly show for the first time that HGF protects the liver from a cholestatic injury.


Assuntos
1-Naftilisotiocianato/toxicidade , Colestase Intra-Hepática/induzido quimicamente , Colestase Intra-Hepática/prevenção & controle , Fator de Crescimento de Hepatócito/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Animais , Colestase Intra-Hepática/patologia , Fator de Crescimento de Hepatócito/farmacologia , Masculino , Camundongos , Estresse Oxidativo/fisiologia
9.
J Cell Physiol ; 235(2): 1637-1648, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31283037

RESUMO

Tuberculosis (TB) is one of the deadliest infectious diseases in humankind history. Although, drug sensible TB is slowly decreasing, at present the rise of TB cases produced by multidrug-resistant (MDR) and extensively drug-resistant strains is a big challenge. Thus, looking for new therapeutic options against these MDR strains is mandatory. In the present work, we studied, in BALB/c mice infected with MDR strain, the therapeutic effect of supra-pharmacological doses of the conventional primary antibiotics rifampicin and isoniazid (administrated by gavage or intratracheal routes), in combination with recombinant human hepatocyte growth factor (HGF). This high dose of antibiotics administered for 3 months, overcome the resistant threshold of the MDR strain producing a significant reduction of pulmonary bacillary loads but induced liver damage, which was totally prevented by the administration of HGF. To address the long-term efficiency of this combined treatment, groups of animals after 1 month of treatment termination were immunosuppressed by glucocorticoid administration and, after 1 month, mice were euthanized, and the bacillary load was determined in lungs. In comparison with animals treated only with a high dose of antibiotics, animals that received the combined treatment showed significantly lower bacterial burdens. Thus, treatment of MDR-TB with very high doses of primary antibiotics particularly administrated by aerial route can produce a very good therapeutic effect, and its hepatic toxicity can be prevented by the administration of HGF, becoming in a new treatment modality for MDR-TB.


Assuntos
Antibióticos Antituberculose/toxicidade , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fator de Crescimento de Hepatócito/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos , Animais , Quimioterapia Combinada , Humanos , Isoniazida/toxicidade , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis , Rifampina/toxicidade
10.
Front Oncol ; 9: 1039, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681577

RESUMO

Growth Differentiation Factor 11 (GDF11), a member of the super family of the Transforming Growth Factor ß, has gained more attention in the last few years due to numerous reports regarding its functions in other systems, which are different to those related to differentiation and embryonic development, such as age-related muscle dysfunction, skin biology, metabolism, and cancer. GDF11 is expressed in many tissues, including skeletal muscle, pancreas, kidney, nervous system, and retina, among others. GDF11 circulating levels and protein content in tissues are quite variable and are affected by pathological conditions or age. Although, GDF11 biology had a lot of controversies, must of them are only misunderstandings regarding the variability of its responses, which are independent of the tissue, grade of cellular differentiation or pathologies. A blunt fact regarding GDF11 biology is that its target cells have stemness feature, a property that could be found in certain adult cells in health and in disease, such as cancer cells. This review is focused to present and analyze the recent findings in the emerging research field of GDF11 function in cancer and metabolism, and discusses the controversies surrounding the biology of this atypical growth factor.

11.
J Cell Physiol ; 234(5): 7213-7223, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30239004

RESUMO

Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of histopathological changes ranging from non-inflammatory intracellular fat deposition to non-alcoholic steatohepatitis (NASH), which may progress into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. Recent data suggest that impaired hepatic cholesterol homeostasis and its accumulation are relevant to the pathogenesis of NAFLD/NASH. Despite a vital physiological function of cholesterol, mitochondrial dysfunction is an important consequence of dietary-induced hypercholesterolemia and was, subsequently, linked to many pathophysiological conditions. The aim in the current study was to evaluate the morphological and molecular changes of cholesterol overload in mouse liver and particularly, in mitochondria, induced by a high-cholesterol (HC) diet for one month. Histopathological studies revealed microvesicular hepatic steatosis and significantly elevated levels of liver cholesterol and triglycerides leading to impaired liver synthesis. Further, high levels of oxidative stress could be determined in liver tissue as well as primary hepatocyte culture. Transcriptomic changes induced by the HC diet involved disruption in key pathways related to cell death and oxidative stress as well as upregulation of genes related to glutathione homeostasis. Impaired liver function could be associated with a decrease in mitochondrial membrane potential and ATP content and significant alterations in mitochondrial dynamics. We demonstrate that cholesterol overload in the liver leads to mitochondrial changes which may render damaged hepatocytes proliferative and resistant to cell death whereby perpetuating liver damage.


Assuntos
Apoptose , Colesterol na Dieta , Dieta Hiperlipídica , Hepatócitos/patologia , Fígado/patologia , Mitocôndrias Hepáticas/patologia , Dinâmica Mitocondrial , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Apoptose/genética , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias Hepáticas/metabolismo , Dinâmica Mitocondrial/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , Fatores de Tempo , Transcriptoma
12.
J Cell Physiol ; 233(12): 9354-9364, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29341114

RESUMO

Acute pancreatitis is a multifactorial disease associated with profound changes of the pancreas induced by release of digestive enzymes that lead to increase in proinflammatory cytokine production, excessive tissue necrosis, edema, and bleeding. Elevated levels of hepatocyte growth factor (HGF) and its receptor c-Met have been observed in different chronic and acute pancreatic diseases including experimental models of acute pancreatitis. In the present study, we investigated the protective effects induced by the recombinant human HGF in a mouse model of cerulein-induced acute pancreatitis. Pancreatitis was induced by 8 hourly administrations of supramaximal cerulein injections (50 µg/kg, ip). HGF treatment (20 µg/kg, iv), significantly attenuated lipase content and amylase activity in serum as well as the degree inflammation and edema overall leading to less severe histologic changes such as necrosis, induced by cerulein. Protective effects of HGF were associated with activation of pro-survival pathways such as Akt, Erk1/2, and Nrf2 and increase in executor survival-related proteins and decrease in pro-apoptotic proteins. In addition, ROS content and lipid peroxidation were diminished, and glutathione synthesis increased in pancreas. Systemic protection was observed by lung histology. In conclusion, our data indicate that HGF exerts an Nrf2 and glutathione-mediated protective effect on acute pancreatitis reflected by a reduction in inflammation, edema, and oxidative stress.


Assuntos
Fator de Crescimento de Hepatócito/uso terapêutico , Pancreatite/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Ceruletídeo , Modelos Animais de Doenças , Glutationa/biossíntese , Fator de Crescimento de Hepatócito/sangue , Fator de Crescimento de Hepatócito/farmacologia , Humanos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Pancreatite/patologia , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Análise de Sobrevida
13.
Oncotarget ; 8(61): 104136-104148, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29262627

RESUMO

Primary liver cancers represent the second leading cause of cancer-related deaths worldwide. Diverse etiological factors include chronic viral hepatitis, aflatoxin and alcohol exposure as well as aberrant liver lipid overload. Cholesterol has been identified as a key inducer of metabolic impairment, oxidative stress and promoter of cellular dysfunction. The aim of this work was to address the oxidative stress-mediated DNA damage induced by cholesterol overload, and its role in the development of hepatocellular carcinoma. C57BL/6 male mice were fed with a high cholesterol diet, followed by a single dose of N-diethylnitrosamine (DEN, 10 µg/g, ip). Reactive oxygen species generation, DNA oxidation, antioxidant and DNA repair proteins were analyzed at different time points. Diet-induced cholesterol overload caused enhanced oxidative DNA damage in the liver and was associated with a decrease in key DNA repair genes as early as 7 days. Interestingly, we found a cell survival response, induced by cholesterol, judged by a decrement in Bax to Bcl2 ratio. Importantly, N-acetyl-cysteine supplementation significantly prevented DNA oxidation damage. Furthermore, at 8 months after DEN administration, tumor growth was significantly enhanced in mice under cholesterol diet in comparison to control animals. Together, these results suggest that cholesterol overload exerts an oxidative stress-mediated effects and promotes the development of liver cancer.

14.
Environ Toxicol ; 32(6): 1669-1678, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28185390

RESUMO

Malathion is one of the most commonly used insecticides. Recent findings have demonstrated that it induces oxidative stress in somatic cells, but there are not enough studies that have demonstrated this effect in germ cells. Malathion impairs porcine oocyte viability and maturation, but studies have not shown how oxidative stress damages maturation and which biochemical mechanisms are affected in this process in cumulus-oocyte complexes (COCs). The aims of the present study were to determine the amount of oxidative stress produced by malathion in porcine COCs matured in vitro, to define how biochemical mechanisms affect this process, and determine whether trolox can attenuate oxidative damage. Sublethal concentrations 0, 750, and 1000 µM were used to evaluate antioxidant enzyme expressions, reactive oxygen species (ROS production), protein oxidation, and lipid peroxidation, among other oxidation products. COCs viability and oocyte maturation decreased in a concentration-dependent manner. Malathion increased Cu, Zn superoxide dismutase (SOD1), glutathione-S-transferase (GST), and glucose 6 phosphate dehydrogenase (G6PD) protein level and decreased glutathione peroxidase (GSH-Px) and catalase (CAT) protein level. Species reactives of oxygen (ROS), protein oxidation and Thiobarbituric acid reactive substances (TBARS) levels increased in COCs exposed to the insecticide, but when COCs were pre-treated with the trolox (50 µM) 30 min before and during malathion exposure, these parameters decreased down to control levels. This study showed that malathion has a detrimental effect on COCs during in vitro maturation, inducing oxidative stress, while trolox attenuated malathion toxicity by decreasing oxidative damage.


Assuntos
Inseticidas/toxicidade , Malation/toxicidade , Oócitos/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Glucosefosfato Desidrogenase/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Oócitos/enzimologia , Oócitos/metabolismo , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Suínos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
15.
Oxid Med Cell Longev ; 2016: 9895176, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27635189

RESUMO

Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.


Assuntos
Colestase/etiologia , Colesterol na Dieta/toxicidade , Fígado/patologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Ductos Biliares/cirurgia , Bilirrubina/análise , Caspase 3/metabolismo , Colestase/patologia , Colesterol/análise , Fígado Gorduroso/etiologia , Glutationa/análise , Imuno-Histoquímica , Icterícia/etiologia , Antígeno Ki-67/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Testes de Função Hepática , Camundongos , Camundongos Endogâmicos C57BL , Mortalidade Prematura , Espécies Reativas de Oxigênio/metabolismo , Triglicerídeos/análise
16.
Oxid Med Cell Longev ; 2016: 7960386, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27143995

RESUMO

Cholesterol overload in the liver has shown toxic effects by inducing the aggravation of nonalcoholic fatty liver disease to steatohepatitis and sensitizing to damage. Although the mechanism of damage is complex, it has been demonstrated that oxidative stress plays a prominent role in the process. In addition, we have proved that hepatocyte growth factor induces an antioxidant response in hepatic cells; in the present work we aimed to figure out the protective effect of this growth factor in hepatocytes overloaded with free cholesterol. Hepatocytes from mice fed with a high-cholesterol diet were treated or not with HGF, reactive oxygen species present in cholesterol overloaded hepatocytes significantly decreased, and this effect was particularly associated with the increase in glutathione and related enzymes, such as γ-gamma glutamyl cysteine synthetase, GSH peroxidase, and GSH-S-transferase. Our data clearly indicate that HGF displays an antioxidant response by inducing the glutathione-related protection system.


Assuntos
Colesterol/toxicidade , Fator de Crescimento de Hepatócito/sangue , Hepatócitos/metabolismo , Hepatócitos/patologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Dieta , Ensaio de Imunoadsorção Enzimática , Glutationa/metabolismo , Hepatócitos/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Proteínas Proto-Oncogênicas c-met/sangue , Espécies Reativas de Oxigênio/metabolismo
17.
Oxid Med Cell Longev ; 2016: 9209825, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26788255

RESUMO

Obesity and alcohol consumption are risk factors for hepatic steatosis, and both commonly coexist. Our objective was to evaluate the effect of ethanol and acetaldehyde on primary hepatocytes obtained from mice fed for two days with a high cholesterol (HC) diet. HC hepatocytes increased lipid and cholesterol content. HC diet sensitized hepatocytes to the toxic effect of ethanol and acetaldehyde. Cyp2E1 content increased with HC diet, as well as in those treated with ethanol or acetaldehyde, while the activity of this enzyme determined in microsomes increased in the HC and in all ethanol treated hepatocytes, HC and CW. Oxidized proteins were increased in the HC cultures treated or not with the toxins. Transmission electron microscopy showed endoplasmic reticulum (ER) stress and megamitochondria in hepatocytes treated with ethanol as in HC and the ethanol HC treated hepatocytes. ER stress determined by PERK content was increased in ethanol treated hepatocytes from HC mice and CW. Nuclear translocation of ATF6 was observed in HC hepatocytes treated with ethanol, results that indicate that lipids overload and ethanol treatment favor ER stress. Oxidative stress, ER stress, and mitochondrial damage underlie potential mechanisms for increased damage in steatotic hepatocyte treated with ethanol.


Assuntos
Acetaldeído/toxicidade , Colesterol/farmacologia , Etanol/toxicidade , Hepatócitos/patologia , Animais , Forma Celular/efeitos dos fármacos , Células Cultivadas , Citocromo P-450 CYP2E1/metabolismo , Dieta Hiperlipídica , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Lipídeos/química , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos
18.
J Mol Recognit ; 29(2): 80-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26370929

RESUMO

The flavonoids are mainly present in Citrus fruits as their glycosyl derivatives. This study was conducted comparing in vitro xanthine oxidase inhibitory activity of the aglycone hesperetin and its glycosylated forms (hesperidin and G-hesperidin) and their effects on the plasma lipid profile and the oxidative-antioxidative system (TBARS and antioxidant enzymes) in rats. The concentrations of the major conjugated metabolites in rat plasma after oral administration of these compounds were also determined. Wistar male rats were randomly assigned to three groups (n=6) supplemented for 30 days with 1 mmol/kg body mass of hesperetin, hesperidin or G-hesperidin. Hesperetin was a stronger xanthine oxidase inhibitor (IC50=53 µM and Ki=17.3 µM) than the glycosylate derivatives. Supplementation with the three compounds led to a lower (more favorable) atherogenic index, and an antioxidant preventive effect from the increase of hepatic superoxide dismutase was observed associated to HT supplementation, possibly because of the higher level of hesperetin-glucuronide in rat plasma.


Assuntos
Antioxidantes/administração & dosagem , Hesperidina/administração & dosagem , Xantina Oxidase/antagonistas & inibidores , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hesperidina/química , Hesperidina/farmacologia , Técnicas In Vitro , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
19.
Rev. bras. ciênc. saúde ; 20(2): 107-114, 2016. ilus, tab
Artigo em Português | LILACS | ID: lil-789419

RESUMO

Introdução: A vida moderna tem permitido facilidade, mas elevado a incidência de sedentarismo e obesidade em países desenvolvidos e inclusive no Brasil. Estudos têm determinado a relação horas de ociosidade e obesidade infantil, entretanto não em nossa região. Objetivo: investigar a prevalência de obesidade através dos indicadores em crianças de ambos os sexos na cidade de Guaxupé/MG e correlacionar com o tempo de atividade de repouso e física. Material e Métodos: 91voluntários, ambos sexos, idade 9,6±1,4 anos, 38,9±9,7Kg,1,4±01m estudantes do Colégio Dom Inácio/Guaxupé foram avaliados: peso corporal, IMC, %G, relação cintura/altura (RCA)e responderam questionário sobre atividades diárias.Resultados: para meninos e meninas, foram respectivamente:IMC peso ideal (70% e 56%), sobre peso (25% e 35%) e obesidade (5% e 9%); %G ótimo (87% e 46%),moderadamente alto (10% e 24%), alto (3% e 21%) e muito alto (0% e 9%); RCA normal (90% e 85%) e risco (10% e145%). Valores médios±(DP) de atividades de repouso e físicas em horas/semana: TV (18,2±10,5 e 17,8±9,2), internet (12,2±11,8 e 11,8±10,5), estudo (18,5±10,2 e 17,8±12,1) e total (48,9±18,2 e 47,4±18,2). Atividades físicas lazer 20,6±11,9 e18,5±11,4); esportes (1,6±1,5 e 1,5±1,4), Educação física (1,9±0,4 e 1,8±0,4) e total (24,1±12,0 e 21,8±11,6). Conclusão: observamos relação positiva entre sedentarismo com %G e RCA e concluímos que os voluntários neste estudo apresentam uma elevada incidência de tempo dispendido em atividades de repouso, representando um estilo de vida sedentário e contribuindo para o sobrepeso e obesidade.


Introduction: Modern life has brought easiness, but also contributed to a high incidence of physical inactivity and obesity in developed and developing countries, including Brazil. Studies have found a relationship between hours of idleness and childhood obesity, but not in our region. Objective: To investigate the prevalence of obesity among children of both sexes in the city of Guaxupe, MG, Brazil, and correlate indicators with their time of rest and physical activity. Material and Methods: 91 volunteers, of both sexes, aged 9.6±1.4 years,38.9±9.7 Kg, 1.4±01 m, students from Dom Inácio School in Guaxupe were assessed as to the following variables: body weight, BMI, %BF, relationship waist/height (RWH). The subjects also answered a questionnaire about daily activities. Results: The following results were found for males and females, respectively: ideal weight - BMI (70% and 56%), overweight (25% and 35%) and obesity (5% and 9%); ideal %BF (87% and46%), moderately high %BF (10% and 24%), high %BF (3%and 21%) and very high %BF (0% and 9%); standard RWH(90% and 85%) and risk (10% and 145%). The mean ± (SD) values of rest and physical activity in hours/week were: TV(18.2 ± 10.5 and 17.8 ± 9.2), internet (12.2 ± 11.8 and 11.8 ±10.5), study (18.5 ± 10.2 and 17.8 ± 12.1) and total (48.9 ± 18.2and 47.4 ± 18.2); leisure physical activity (20.6 ± 11.9 and 18.5± 11.4), sports (1.6 ± 1.5 and 1.5 ± 1.4), physical education (1.9± 0.4 and 1.8 ± 0.4) and total (24.1 ± 12.0 and 21 8 ± 11.6). Conclusion: we observed a positive relationship between physical inactivity and %BF and RWH. It may be concluded that the volunteers in this study have a high incidence of time spent in resting activities, which indicates a sedentary lifestyle and may contribute to overweight and obesity.


Assuntos
Humanos , Masculino , Feminino , Criança , Saúde da Criança , Obesidade Infantil , Comportamento Sedentário
20.
Rev. bras. enferm ; 68(5): 791-796, set.-out. 2015.
Artigo em Português | LILACS, BDENF - Enfermagem | ID: lil-763180

RESUMO

RESUMOObjetivo:analisar a concepção dos adolescentes a respeito da espiritualidade, religiosidade e crenças pessoais presentes em suas vidas devido ao câncer e como estratégia de enfrentamento da doença.Método:pesquisa qualitativa, do tipo descritiva e exploratória. Os dados foram coletados através de um roteiro de entrevista semi-estruturado, as categorias foram definidas segundo a análise de conteúdo.Resultados:participaram nove adolescentes que estavam em tratamento oncológico em duas instituições na cidade de Uberaba, Minas Gerais. Os dados foram sistematizados em quatro categorias: história espiritual do indivíduo; fé e crença; importância da espiritualidade em sua vida; e a comunidade enquanto apoio espiritual. A maioria dos adolescentes referiu a espiritualidade importante no enfrentamento a doença, especialmente a partir de rituais religiosos e apoio da comunidade.Conclusão:a espiritualidade gera esperança para os adolescentes, auxiliando no enfrentamento das dificuldades relacionadas ao câncer e na busca pelo sentido da vida.


RESUMENObjetivo:examinó la percepción de los adolescentes acerca de la espiritualidad, la religión y las creencias personales en sus vidas por el cáncer y una posible estrategia para hacer frente a la enfermedad.Método:se realizó una investigación cualitativa, descriptivo y exploratorio, del guión de la entrevista semi-estructurada sobre la base de las literaturas afi nes, lo que permitió la defi nición de categorías, analizadas desde la perspectiva del análisis de contenido.Resultados:asistió a nueve jóvenes que fueron sometidos a tratamiento contra el cáncer en las dependencias de ambas instituciones ubicadas en la ciudad de Uberaba, Minas Gerais, Brasil. A partir del análisis fue posible sistematizar de acuerdo a cuatro categorías: historia espiritual de la persona, la fe y las creencias; importancia de la espiritualidad en sus vidas, y la comunidad como apoyo espiritual. La mayoría de los adolescentes informó espiritualidad como acontecimientos actuales e importantes relacionados con la enfermedad, especialmente de los rituales religiosos y apoyo comunitario.Conclusión:la espiritualidad parece emerger como un componente generador de esperanza para los jóvenes, ayudando a hacer frente a las dificultades relacionadas con el cáncer y la búsqueda del sentido de la vida.


ABSTRACTObjective:to examine adolescents’ perception about spirituality, religion and personal beliefs in their lives due to cancer and a possible strategy for coping with the disease.Method:qualitative research, both descriptive and exploratory. The data were collected by means of a personal semi-structured interview, and the categories were analyzed by content analyzes.Results:nine adolescents who were undergoing cancer treatment at one of the two institutions located Uberaba, Brazil, participated in the study. Based on the analysis and interpretation of results, it was possible to systematize them according to four categories: spiritual history of the individual; faith and belief; importance of spirituality in their lives, and the community acting as a spiritual supporter. Most adolescents referred to spirituality as being an important tool for dealing with the disease, especially concerning religious rituals and community support.Conclusion:spirituality creates hope for adolescents, which helps them to cope with cancer-related diffi culties and contribute to the search for the meaning of life.

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