RESUMO
Obesity has emerged as a leading cause of death in the last few decades, mainly due to associated cardiovascular diseases. Obesity, inflammation, and insulin resistance are strongly interlinked. Lisofylline (LSF), an anti-inflammatory agent, demonstrated protection against type 1 diabetes, as well as reduced obesity-induced insulin resistance and adipose tissue inflammation. However, its role in mitigating cardiac inflammation associated with obesity is not well studied. Mice were divided into 4 groups; the first group was fed regular chow diet, the second was fed regular chow diet and treated with LSF, the third was fed high fat diet (HFD), and the fourth was fed HFD and treated with LSF. Cardiac inflammation was interrogated via expression levels of TNF α, interleukins 6 and 10, phosphorylated STAT4 and lipoxygenases 12 and 12/15. Apoptosis and expression of the survival gene, AMPK, were also evaluated. We observed that LSF alleviated obesity-induced cardiac injury indirectly by improving both pancreatic ß-cell function and insulin sensitivity, as well as, directly via upregulation of cardiac AMPK expression and downregulation of cardiac inflammation and apoptosis. LSF may represent an effective therapy targeting obesity-induced metabolic and cardiovascular complications.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Coração/fisiologia , Inflamação/metabolismo , Insulina/metabolismo , Miocárdio/enzimologia , Miocárdio/metabolismo , Obesidade/metabolismo , Pentoxifilina/análogos & derivados , Tecido Adiposo/metabolismo , Animais , Apoptose , Glicemia/metabolismo , Peso Corporal , Modelos Animais de Doenças , Resistência à Insulina/fisiologia , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pentoxifilina/farmacologia , Transdução de Sinais , Regulação para CimaRESUMO
Metabolic (Met) syndrome is characterized by hypertension, insulin resistance and dyslipidaemia with high risk of cardiovascular disease. Endoplasmic reticulum (ER) stress is a key contributor in the pathogenesis of Met syndrome. The current study investigates the effect of Tauroursodeoxycholate (TUDCA), an ER stress inhibitor, on Met syndrome-induced cardiovascular complications and the possible underlying signalling mechanisms. Met syndrome was induced in rats, which were then treated with TUDCA. Body weight, blood pressure, glucose tolerance and insulin tolerance tests were performed. ER stress, survival and oxidative stress markers were measured in heart and aorta tissue. The results showed that TUDCA improved metabolic parameters in rats with Met syndrome. Treatment mitigated the Met syndrome-induced cardiovascular complications through upregulating survival markers and downregulating ER and oxidative stress markers. These results highlight the protective effect of ER stress inhibition as a potential target in the management of cardiovascular complications associated with Met syndrome.
Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Animais , Biomarcadores , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Endotélio/metabolismo , Imuno-Histoquímica , Síndrome Metabólica/etiologia , Fenótipo , Ratos , Ácido Tauroquenodesoxicólico/farmacologiaRESUMO
Multiple organs, including the testes, are damaged by iron overload. It has been shown that N-acetyl cysteine (NAC) influences oxidative stress in iron overload. The present study aimed to evaluate the roles of acetylated peptide (AOP) and NAC in the inhibition of iron-overload induced-testicular damage. At the beginning of the experiment, NAC (150 mg /kg) was given for a week to all 40 rats. Then, four groups were formed by dividing the animals (10 rats/group). Group I included healthy control rats. Group II (iron overload) was given intraperitoneal iron dextran (60 mg/kg/day) 5 days a week for 4 weeks. Group III (NAC) was given NAC orally at a dose of 150 mg/kg/day for 4 weeks in addition to iron dextran. Group IV (AOP) was given AOP orally at a dose of 150 mg/kg/day for 4 weeks besides iron dextran. When the experiment time was over, testosterone serum level, testicular B cell lymphoma-2 (BCL-2) and protein kinase B (PKB) protein levels, nuclear factor kappa-B (NF-κB), and Beclin1 mRNA expression levels, and malondialdehyde (MDA), and reduced glutathione (GSH) were determined by ELISA, quantitative reverse transcription-PCR, and chemical methods. Finally, histopathological examinations and immunohistochemical detection of claudin-1 and CD68 were performed. The iron overload group exhibited decreased testosterone, BCL-2, PKB, claudin-1, and GSH and increased MDA, NF-κB, Beclin1, and CD68, while both NAC and AOP treatments protected against the biochemical and histopathological disturbances occurring in the iron overload model. We concluded that NAC and AOP can protect against testes damage by iron overload via their antioxidant, anti-inflammatory, antiapoptotic, and ant-autophagic properties. The NAC and AOP may be used as preventative measures against iron overload-induced testicular damage.
Assuntos
Acetilcisteína , Sobrecarga de Ferro , Masculino , Ratos , Animais , Acetilcisteína/farmacologia , Acetilcisteína/metabolismo , Testículo , NF-kappa B/metabolismo , Proteína Beclina-1/metabolismo , Claudina-1/metabolismo , Dextranos/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Glutationa/metabolismo , Morte Celular , Testosterona/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ferro/metabolismoRESUMO
The study included 32 women with PAS and 20 with normally implanted placenta as a control group. Vascular endothelial cell growth factor (VEGF), Soluble FMS Like Tyrosine Kinase (sFLT-1/sVEGFR1), and Endoglin (ENG) were measured in placenta tissue by ELISA. Granzyme B (GrzB) expression in trophoblastic and stromal mesenchymal cells was evaluated by immunohistochemistry. MAIT, NK, and NKT cells were assessed in blood and placenta by flow cytometry. Alterations were observed in levels of MAIT cells, NK cell subsets, and NKT cells in patients compared with controls. Several significant correlations were detected between these cells and GrzB scores, VEGF, ENG, and sFLT-1 levels. This is the first study analysing these cells in PAS patients and correlating their levels with changes in some angiogenic and antiangiogenic factors implicated in trophoblast invasion and with GrzB distribution in trophoblast and stroma. Interrelation between these cells probably plays an important role in pathogenesis of PAS.
Assuntos
Células T Matadoras Naturais , Placenta Acreta , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Placenta Acreta/metabolismo , Células T Matadoras Naturais/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Endoglina/metabolismo , Pré-Eclâmpsia/metabolismoRESUMO
Morphologic design of nanomaterials for a diversity of biomedical applications is of increasing interest. The aim of the current study is to construct therapeutic gold nanoparticles of different morphologies and investigate their effect on ocular retention and intraocular pressure in a glaucoma rabbit model. Poly(lactic-co-glycolic acid) (PLGA)-coated nanorods and nanospheres have been synthesized and loaded with carbonic anhydrase inhibitor (CAI), and characterized in vitro for their size, zeta potential and encapsulation efficiency. Nanosized PLGA-coated gold nanoparticles of both morphologies demonstrated high entrapment efficiency (Ë 98%) for the synthesized CAI and the encapsulation of the drug into the developed nanoparticles was confirmed via Fourier transform-infrared spectroscopy. In vivo studies revealed a significant reduction in intraocular pressure upon instillation of drug-loaded nanogold formulations compared to the marketed eye drops. Spherical nanogolds exhibited a superior efficacy compared to the rod-shaped counterparts, probably due to the enhanced ocular retention of spherical nanogolds within collagen fibers of the stroma, as illustrated by transmission electron microscopy imaging. Normal histological appearance was observed for the cornea and retina of the eyes treated with spherical drug-loaded nanogolds. Hence, incorporation of a molecularly-designed CAI into nanogold of tailored morphology may provide a promising strategy for management of glaucoma.
Assuntos
Glaucoma , Nanopartículas Metálicas , Nanopartículas , Animais , Coelhos , Pressão Intraocular , Inibidores da Anidrase Carbônica/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ouro/uso terapêutico , Glaucoma/tratamento farmacológico , Nanopartículas/química , Córnea , Portadores de Fármacos/química , Tamanho da PartículaRESUMO
The sustainable application of an up-flow anaerobic baffled reactor (UABR) to treat real paper and cardboard industrial effluent (PCIE) containing bronopol (2-bromo-2-nitropropan-1, 3-diol) was investigated. At a hydraulic retention time (HRT) of 11.7 h and a bronopol concentration of 7.0 mg L-1, the removal efficiencies of total chemical oxygen demand (CODtotal), CODsoluble, CODparticulate, total suspended solids (TSS), volatile suspended solids (VSS), carbohydrates, and proteins were 55.3 ± 5.2%, 26.8 ± 2.3%, 94.4 ± 4.6%, 89.4 ± 2.6%, 84.5 ± 3.2%, 72.1 ± 1.8%, and 22.4 ± 1.8%, respectively. The conversion of complex organics (e.g., carbohydrates and proteins) into bio-methane (CH4) was assisted via enzyme activities of, in U (100 mL)-1, α-amylase (224-270), α-xylanase (171-188), carboxymethyl cellulase (CM-cellulase) (146-187), polygalacturonase (56-126), and protease (67,000-75300). The acidogenic condition was dominant at a short HRT of 2.9 h, where methane yield dropped by 32.5%. Under this condition, the growth of methanogenic bacteria could be inhibited by volatile fatty acids (VFA) accumulation. The analysis of Fourier-transform infrared (FTIR) spectra detected peaks relevant to methylene and nitro groups in the sludge samples, suggesting that entrapment/adsorption by the sludge bed could be a major mechanism for removing bronopol. The economic feasibility of UABR, as proposed to receive 100 m3 d-1 of PCIE, showed a payback period (profits from environmental benefits, biogas recovery, and carbon credit) of 7.6 yr. The study outcomes showed a high connection to the environmental-, economic-, and social-related sustainable development goals (SDGs).
Assuntos
Eliminação de Resíduos Líquidos , Águas Residuárias , Anaerobiose , Reatores Biológicos , Indústria Manufatureira , Metano , EsgotosRESUMO
Tramadol is an opioid extensively used to treat moderate to severe pain; however, prolonged therapy is associated with several tissues damage. Chronic use of tramadol was linked to increased hospitalizations due to cardiovascular complications. Limited literature has described the effects of tramadol on the cardiovascular system, so we sought to investigate these actions and elucidate the underlying mechanisms. Mice received tramadol hydrochloride (40 mg/kg body weight) orally for 4 successive weeks. Oxidative stress, inflammation, and cardiac toxicity were assessed. In addition, eNOS expression was evaluated. Our results demonstrated marked histopathological alteration in heart and aortic tissues after exposure to tramadol. Tramadol upregulated the expression of oxidative stress and inflammatory markers in mice heart and aorta, whereas downregulated eNOS expression. Tramadol caused cardiac damage shown by the increase in LDH, Troponin I, and CK-MB activities in serum samples. Overall, these results highlight the risks of tramadol on the cardiovascular system.
Assuntos
Analgésicos Opioides/efeitos adversos , Endotélio Vascular/efeitos dos fármacos , Coração/efeitos dos fármacos , Miocardite/complicações , Tramadol/efeitos adversos , Analgésicos Opioides/administração & dosagem , Animais , Citocinas/metabolismo , Regulação para Baixo , Endotélio Vascular/fisiopatologia , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Miocardite/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Tramadol/administração & dosagem , Regulação para CimaRESUMO
Genetic and epigenetic factors contribute equally to the pathogenesis of type 1 diabetes mellitus. Sodium butyrate (NaB) has been reported to improve glucose homeostasis by modulation of the p38/ERK MAPK pathway. This work aims to evaluate the effect of NaB on the ultrastructure of pancreatic ß-cells and the PI3/AKT pathway. Juvenile albino male rats were used to establish a type 1 diabetes model using streptozotocin injection and NaB in a pre- and post-treatment schedule. Plasma glucose, insulin levels, and glucose tolerance were evaluated. Light and electron microscopy and immunohistochemistry were performed using Ki-67, caspase-3, and insulin. NaB treatment resulted in a significant improvement in plasma glucose levels, plasma insulin levels/expression, and ameliorated diabetes-induced histological alternations. Additionally, it increased the expression of phosphorylated AKT. These findings provide evidence that NaB may be useful in the treatment of juvenile diabetes.