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ABSTRACT Purpose To evaluate the morphological and stereological parameters of the testicles in mice exposed to bisphenol S and/or high-fat diet-induced obesity. Material and Methods Forty adult male C57BL/6 mice were fed a standard diet (SC) or high-fat diet (HF) for a total of 12 weeks. The sample was randomly divided into 4 experimental groups with 10 mices as follows: a) SC - animals fed a standard diet; b) SC-B - animals fed a standard diet and administration of BPS (25 μg/kg of body mass/day) in drinking water; c) HF: animals fed a high-fat diet; d) HF-B - animals fed a high-fat diet and administration of BPS (25 μg/Kg of body mass/day) in drinking water. BPS administration lasted 12 weeks, following exposure to the SC and HF diets. BPS was diluted in absolute ethanol (0.1%) and added to drinking water (concentration of 25 μg/kg body weight/day). The animals were euthanized, and the testes were processed and stained with hematoxylin and eosin (H&E) for morphometric and stereological parameters, including density of seminiferous tubules per area, length density and total length of seminiferous tubules, height of the tunica albuginea and the diameter of the seminiferous tubules. The images were captured with an Olympus BX51 microscope and Olympus DP70 camera. The stereological analysis was done with the Image Pro and Image J programs. Means were statistically compared using ANOVA and the Holm-Sidak post-test (p<0.05). Results The seminiferous tubule density per area reduced in all groups when compared with SC samples (p<0.001): HF (40%), SC-B 3(2%), and HF-B (36%). Length density was reduced significantly (p<0.001) in all groups when compared with SC group: HF (40%), SC-B (32%), and HF-B (36%). The seminiferous tubule total length was reduced (p<0.001) when compared to f HF (28%) and SC-B (26%) groups. The tubule diameter increased significantly (p<0.001) only when we compared the SC group with SC (54%) an SC-B (25%) groups and the tunica thickness increased significantly only in HF group (117%) when compared with SC-B (20%) and HF-B 31%. Conclusion Animals exposed to bisphenol S and/or high-fat diet-induced obesity presented important structural alterations in testicular morphology.
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Bisphenol S (BPS) is widely used in the manufacture products and increase the risk of cardiovascular diseases. The effect of the association between obesity and BPS on cardiac outcomes is still unknown. Male C57BL/6 mice were divided into standard chow diet (SC; 15 kJ/g), standard chow diet + BPS (SCB), high-fat diet (HF; 21 kJ/g), and high-fat diet + BPS (HFB). Over 12 weeks, the groups were exposed to BPS through drinking water (dose: 25 µg/kg/day) and/or a HF diet. We evaluated: body mass (BM), total cholesterol, systolic blood pressure (SBP), left ventricle (LV) mass, and cardiac remodeling. In the SCB group, BM, total cholesterol, and SBP increase were augmented in relation to the SC group. In the HF and HFB groups, these parameters were higher than in the SC and SCB groups. Cardiac hypertrophy was evidenced by augmented LV mass and wall thickness, and ANP protein expression in all groups in comparison to the SC group. Only the HFB group had a thicker LV wall than SCB and HF groups, and increased cardiomyocyte area when compared with SC and SCB groups. Concerning cardiac fibrosis, SCB, HF, and HFB groups presented higher interstitial collagen area, TGFß, and α-SMA protein expression than the SC group. Perivascular collagen area was increased only in the HF and HFB groups than SC group. Higher IL-6, TNFα, and CD11c protein expression in all groups than the SC group evidenced inflammation. All groups had elevated CD36 and PPARα protein expression in relation to the SC group, but only HF and HFB groups promoted cardiac steatosis with increased perilipin 5 protein expression than the SC group. BPS exposure alone promoted cardiac remodeling with pathological concentric hypertrophy, fibrosis, and inflammation. Diet-induced remodeling is aggravated when associated with BPS, with marked hypertrophy, alongside fibrosis, inflammation, and lipid accumulation.
Assuntos
Cardiomegalia , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Fenóis , Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Camundongos , Fenóis/toxicidade , Remodelação Ventricular/efeitos dos fármacos , SulfonasRESUMO
Tributyltin (TBT) is an organotin compound that has several adverse health effects, including the development of obesity. Although obesity is strongly associated with adipose redox imbalance, there is a lack of information on whether TBT promotes a pro-oxidative environment in WAT. Thus, adult male Wistar rats were randomly exposed to either vehicle (ethanol 0.4%) or TBT (1000 ng/kg) for 30 days. Body and fat pad masses, visceral fat morphology, lipid peroxidation, protein carbonylation, redox status markers, and catalase activity were evaluated. TBT promoted increased adiposity and visceral fat, with hypertrophic adipocytes, but did not alter body mass and subcutaneous fat. ROS production and lipid peroxidation were elevated in TBT group, as well as catalase protein expression and activity, although protein oxidation and glutathione peroxidase protein expression remained unchanged. In conclusion, this is the first study to demonstrate that subacute TBT administration leads to visceral adipose redox imbalance, with increased oxidative stress. This enlights the understanding of the metabolic toxic outcomes of continuous exposure to TBT in mammals.
Assuntos
Adiposidade , Catalase , Gordura Intra-Abdominal , Peroxidação de Lipídeos , Oxirredução , Estresse Oxidativo , Ratos Wistar , Compostos de Trialquitina , Animais , Masculino , Compostos de Trialquitina/toxicidade , Oxirredução/efeitos dos fármacos , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Adiposidade/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Catalase/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Glutationa Peroxidase/metabolismoRESUMO
PURPOSE: To evaluate the morphological and stereological parameters of the testicles in mice exposed to bisphenol S and/or high-fat diet-induced obesity. MATERIAL AND METHODS: Forty adult male C57BL/6 mice were fed a standard diet (SC) or high-fat diet (HF) for a total of 12 weeks. The sample was randomly divided into 4 experimental groups with 10 mices as follows: a) SC - animals fed a standard diet; b) SC-B - animals fed a standard diet and administration of BPS (25 µg/kg of body mass/day) in drinking water; c) HF: animals fed a high-fat diet; d) HF-B - animals fed a high-fat diet and administration of BPS (25 µg/Kg of body mass/day) in drinking water. BPS administration lasted 12 weeks, following exposure to the SC and HF diets. BPS was diluted in absolute ethanol (0.1%) and added to drinking water (concentration of 25 µg/kg body weight/day). The animals were euthanized, and the testes were processed and stained with hematoxylin and eosin (H&E) for morphometric and stereological parameters, including density of seminiferous tubules per area, length density and total length of seminiferous tubules, height of the tunica albuginea and the diameter of the seminiferous tubules. The images were captured with an Olympus BX51 microscope and Olympus DP70 camera. The stereological analysis was done with the Image Pro and Image J programs. Means were statistically compared using ANOVA and the Holm-Sidak post-test (p<0.05). RESULTS: The seminiferous tubule density per area reduced in all groups when compared with SC samples (p<0.001): HF (40%), SC-B 3(2%), and HF-B (36%). Length density was reduced significantly (p<0.001) in all groups when compared with SC group: HF (40%), SC-B (32%), and HF-B (36%). The seminiferous tubule total length was reduced (p<0.001) when compared to f HF (28%) and SC-B (26%) groups. The tubule diameter increased significantly (p<0.001) only when we compared the SC group with SC (54%) an SC-B (25%) groups and the tunica thickness increased significantly only in HF group (117%) when compared with SC-B (20%) and HF-B 31%. CONCLUSION: Animals exposed to bisphenol S and/or high-fat diet-induced obesity presented important structural alterations in testicular morphology.
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Compostos Benzidrílicos , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Obesidade , Fenóis , Testículo , Masculino , Animais , Dieta Hiperlipídica/efeitos adversos , Testículo/efeitos dos fármacos , Testículo/patologia , Fenóis/toxicidade , Obesidade/induzido quimicamente , Distribuição Aleatória , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Modelos Animais de Doenças , Camundongos , Reprodutibilidade dos Testes , SulfonasRESUMO
The renin-angiotensin system (RAS) is an endocrine system composed of two main axes: the classical and the counterregulatory, very often displaying opposing effects. The classical axis, primarily mediated by angiotensin receptors type 1 (AT1R), is linked to obesity-associated metabolic effects. On the other hand, the counterregulatory axis appears to exert antiobesity effects through the activation of two receptors, the G protein-coupled receptor (MasR) and Mas-related receptor type D (MrgD). The local RAS in adipose organ has prompted extensive research into white adipose tissue and brown adipose tissue (BAT), with a key role in regulating the cellular and metabolic plasticity of these tissues. The MasR activation favors the brown plasticity signature in the adipose organ by improve the thermogenesis, adipogenesis, and lipolysis, decrease the inflammatory state, and overall energy homeostasis. The MrgD metabolic effects are related to the maintenance of BAT functionality, but the signaling remains unexplored. This review provides a summary of RAS counterregulatory actions triggered by Mas and MrgD receptors on adipose tissue plasticity. Focus on the effects related to the morphology and function of adipose tissue, especially from animal studies, will be given targeting new avenues for treatment of obesity-associated metabolic effects.
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Tecido Adiposo , Proto-Oncogene Mas , Receptores Acoplados a Proteínas G , Sistema Renina-Angiotensina , Animais , Humanos , Tecido Adiposo/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Metabolismo Energético , Obesidade/metabolismo , Obesidade/patologia , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina/fisiologia , Transdução de SinaisRESUMO
Obesity over-activates the classical arm of the renin-angiotensin system (RAS), impairing skeletal muscle remodeling. We aimed to compare the effect of exercise training and enalapril, an angiotensin-converting enzyme inhibitor, on RAS modulation in the skeletal muscle of obese animals. Thus, we divided C57BL/6 mice into two groups: standard chow (SC) and high-fat (HF) diet for 16 weeks. At the eighth week, the HF-fed animals were divided into four subgroups-sedentary (HF), treated with enalapril (HF-E), exercise training protocol (HF-T), and combined interventions (HF-ET). After 8 weeks of treatment, we evaluated body mass and index (BMI), body composition, exercise capacity, muscle morphology, and skeletal muscle molecular markers. All interventions resulted in lower BMI and attenuation of overactivation in the classical arm, while favoring the B2R in the bradykinin receptors profile. This was associated with reduced apoptosis markers in obese skeletal muscles. The HF-T group showed an increase in muscle mass and expression of biosynthesis markers and a reduction in expression of degradation markers and muscle fiber atrophy due to obesity. These findings suggest that the combination intervention did not have a synergistic effect against obesity-induced muscle remodeling. Additionally, the use of enalapril impaired muscle's physiological adaptations to exercise training.
Assuntos
Inibidores da Enzima Conversora de Angiotensina , Enalapril , Camundongos Endogâmicos C57BL , Músculo Esquelético , Obesidade , Condicionamento Físico Animal , Animais , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/fisiopatologia , Condicionamento Físico Animal/fisiologia , Camundongos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Enalapril/farmacologia , Dieta Hiperlipídica/efeitos adversos , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologiaRESUMO
Overactivation of the classic arm of the renin-angiotensin system (RAS) is one of the main mechanisms involved in obesity-related cardiac remodeling, and a possible relationship between RAS and ER stress in the cardiovascular system have been described. Thus, the aim of this study is to evaluate if activating the protective arm of the RAS by ACE inhibition or aerobic exercise training could overturn diet-induced pathological cardiac hypertrophy by attenuating ER stress. Male C57BL/6 mice were fed a control (SC) or a high-fat diet (HF) for 16 weeks. In the 8th week, HF-fed animals were randomly divided into HF, enalapril treatment (HF-En), and aerobic exercise training (HF-Ex) groups. Body mass (BM), food and energy intake, plasma analyzes, systolic blood pressure (SBP), physical conditioning, and plasma ACE and ACE2 activity were evaluated. Cardiac morphology, and protein expression of hypertrophy, cardiac metabolism, RAS, and ER stress markers were assessed. Data presented as mean ± standard deviation and analyzed by one-way ANOVA with Holm-Sidak post-hoc. HF group had increased BM and SBP, and developed pathological concentric cardiac hypertrophy, with overactivation of the classic arm of the RAS, and higher ER stress. Both interventions reverted the increase in BM, and SBP, and favored the protective arm of the RAS. Enalapril treatment improved pathological cardiac hypertrophy with partial reversal of the concentric pattern, and slightly attenuated cardiac ER stress. In contrast, aerobic exercise training induced physiological eccentric cardiac hypertrophy, and fully diminished ER stress.
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BACKGROUND: Despite the importance of women in clinical research, no assessment has been made of the fraction of women in a leadership positions in the Cardiology journals of the SBC. OBJECTIVES: To assess the fraction of female authors in the International Journal of Cardiovascular Sciences (IJCS) and the Arquivos Brasileiros de Cardiologia (ABC Cardiol) over the last decades. METHODS: We searched the original articles of the ABC Cardiol, from 2000 to 2019, and of the IJCS, from 2010 to 2019. We surveyed the number of first and senior female authors and the total number of original articles from 2010 to 2019. We calculated the total proportion of female authorship and compared the first quinquennium with the second. Only data from the ABC Cardiol were analyzed to assess the temporal evolution of the two decades. We used the chi-square test to assess the differences within each journal and between them. The IBM® SPSS® software was used in the analyses. The level of significance adopted was 5%. RESULTS: From 2010 to 2019, 1,157 original articles were published in the ABC Cardiol and 398 in the IJCS. We observed that women are more prevalent as first authors in the IJCS compared to the ABC Cardiol, but men prevail as senior authors in both journals. From 2010 to 2019, there was no significant change in the proportion of female authorship. Throughout the decades analyzed for the ABC Cardiol, there was a projection of linear growth of female authorship, with the slope of the line being greater in the first authorship than in senior authorship. CONCLUSIONS: There is gender disparity, with lower female representativeness in authorship in the articles from the Brazilian Cardiology journals analyzed: Arquivos Brasileiros de Cardiologia and International Journal of Cardiovascular Sciences. We believe that based on these results, more efforts should be implemented in the search for gender equity in the cardiology scientific production published by these journals.
FUNDAMENTO: Apesar da importância das mulheres na pesquisa clínica, não existe uma avaliação da fração de mulheres em posições de autoria nos periódicos de cardiologia da SBC. OBJETIVOS: Avaliar a fração de mulheres autoras na International Journal of Cardiovascular Sciences (IJCS) e nos Arquivos Brasileiros de Cardiologia (ABC Cardiol) nas últimas décadas. MÉTODOS: Realizamos busca dos artigos originais dos ABC Cardiol, entre 2000 e 2019, e da IJCS, entre 2010 e 2019. Foi feito levantamento do número de primeiras e últimas autoras e do total de artigos originais de 2010 a 2019. Calculamos as proporções totais de autorias femininas e comparamos o primeiro quinquênio com o segundo. Para avaliar a evolução temporal das duas décadas, analisamos apenas dados dos ABC Cardiol. Utilizamos o teste Qui-quadrado para analisar as diferenças dentro de cada revista e entre ambas. O software IBM® SPSS® foi utilizado nas análises. O nível de significância adotado foi de 5%. RESULTADOS: De 2010 a 2019, foram publicados 1157 artigos originais nos ABC Cardiol e 398 na IJCS. Observamos que as mulheres têm maior predominância como primeiras autoras na IJCS em relação aos ABC Cardiol, mas os homens predominam como últimos autores em ambos. De 2010 a 2019, não houve modificação significativa na proporção de autorias femininas. Ao longo das décadas analisadas para os ABC Cardiol, houve projeção de crescimento linear de autorias femininas, sendo que a inclinação da reta é maior na projeção da primeira autoria que na autoria sênior. CONCLUSÕES: Há disparidade de gênero com menor representatividade feminina nas autorias dos artigos dos periódicos cardiológicos brasileiros analisados: Arquivos Brasileiros de Cardiologia e International Journal of Cardiovascular Sciences. Acreditamos que a partir destes resultados mais esforços devam ser implementados em busca de equidade de gênero na produção científica cardiológica veiculada por estes periódicos.
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Cardiologia , Publicações Periódicas como Assunto , Masculino , Humanos , Feminino , Autoria , BrasilRESUMO
Resumo Fundamento: Apesar da importância das mulheres na pesquisa clínica, não existe uma avaliação da fração de mulheres em posições de autoria nos periódicos de cardiologia da SBC. Objetivos: Avaliar a fração de mulheres autoras na International Journal of Cardiovascular Sciences (IJCS) e nos Arquivos Brasileiros de Cardiologia (ABC Cardiol) nas últimas décadas. Métodos: Realizamos busca dos artigos originais dos ABC Cardiol, entre 2000 e 2019, e da IJCS, entre 2010 e 2019. Foi feito levantamento do número de primeiras e últimas autoras e do total de artigos originais de 2010 a 2019. Calculamos as proporções totais de autorias femininas e comparamos o primeiro quinquênio com o segundo. Para avaliar a evolução temporal das duas décadas, analisamos apenas dados dos ABC Cardiol. Utilizamos o teste Qui-quadrado para analisar as diferenças dentro de cada revista e entre ambas. O software IBM® SPSS® foi utilizado nas análises. O nível de significância adotado foi de 5%. Resultados: De 2010 a 2019, foram publicados 1157 artigos originais nos ABC Cardiol e 398 na IJCS. Observamos que as mulheres têm maior predominância como primeiras autoras na IJCS em relação aos ABC Cardiol, mas os homens predominam como últimos autores em ambos. De 2010 a 2019, não houve modificação significativa na proporção de autorias femininas. Ao longo das décadas analisadas para os ABC Cardiol, houve projeção de crescimento linear de autorias femininas, sendo que a inclinação da reta é maior na projeção da primeira autoria que na autoria sênior. Conclusões: Há disparidade de gênero com menor representatividade feminina nas autorias dos artigos dos periódicos cardiológicos brasileiros analisados: Arquivos Brasileiros de Cardiologia e International Journal of Cardiovascular Sciences. Acreditamos que a partir destes resultados mais esforços devam ser implementados em busca de equidade de gênero na produção científica cardiológica veiculada por estes periódicos.
Abstract Background: Despite the importance of women in clinical research, no assessment has been made of the fraction of women in a leadership positions in the Cardiology journals of the SBC. Objectives: To assess the fraction of female authors in the International Journal of Cardiovascular Sciences (IJCS) and the Arquivos Brasileiros de Cardiologia (ABC Cardiol) over the last decades. Methods: We searched the original articles of the ABC Cardiol, from 2000 to 2019, and of the IJCS, from 2010 to 2019. We surveyed the number of first and senior female authors and the total number of original articles from 2010 to 2019. We calculated the total proportion of female authorship and compared the first quinquennium with the second. Only data from the ABC Cardiol were analyzed to assess the temporal evolution of the two decades. We used the chi-square test to assess the differences within each journal and between them. The IBM® SPSS® software was used in the analyses. The level of significance adopted was 5%. Results: From 2010 to 2019, 1,157 original articles were published in the ABC Cardiol and 398 in the IJCS. We observed that women are more prevalent as first authors in the IJCS compared to the ABC Cardiol, but men prevail as senior authors in both journals. From 2010 to 2019, there was no significant change in the proportion of female authorship. Throughout the decades analyzed for the ABC Cardiol, there was a projection of linear growth of female authorship, with the slope of the line being greater in the first authorship than in senior authorship. Conclusions: There is gender disparity, with lower female representativeness in authorship in the articles from the Brazilian Cardiology journals analyzed: Arquivos Brasileiros de Cardiologia and International Journal of Cardiovascular Sciences. We believe that based on these results, more efforts should be implemented in the search for gender equity in the cardiology scientific production published by these journals.
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AIMS: Endoplasmic reticulum (ER) stress poses a new pathological mechanism for metabolic-associated fatty liver disease (MAFLD). MAFLD treatment has encompassed renin-angiotensin system (RAS) blockers and aerobic exercise training, but their association with hepatic ER stress is not well known. Therefore, we aimed to compare the effects of hepatic RAS modulation by enalapril and/or aerobic exercise training over ER stress in MAFLD caused by a diet-induced obesity model. MAIN METHODS: C57BL/6 mice were fed a standard-chow (CON, n = 10) or a high-fat (HF, n = 40) diet for 8 weeks. HF group was then randomly divided into: HF (n = 10), HF + Enalapril (EN, n = 10), HF + Aerobic exercise training (AET, n = 10), and HF + Enalapril+Aerobic exercise training (EN + AET, n = 10) for 8 more weeks. Body mass (BM) and glucose profile were evaluated. In the liver, ACE and ACE2 activity, morphology, lipid profile, and protein expression of ER stress and metabolic markers were assessed. KEY FINDINGS: Both enalapril and aerobic exercise training provided comparable efficacy in improving diet-induced MAFLD through modulation of RAS and ER stress, but the latter was more efficient in improving ER stress, liver damage and metabolism. SIGNIFICANCE: This is the first study to evaluate pharmacological (enalapril) and non-pharmacological (aerobic exercise training) RAS modulators associated with ER stress in a diet-induced MAFLD model.