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1.
Biol Trace Elem Res ; 180(2): 255-264, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28409410

RESUMO

Hyperlipidemia is one of the major risk factors for atherosclerosis and ischemic heart disease. Chromium (Cr) mineral is playing a crucial role in glucose and lipid homeostasis. The aim of this study was to evaluate the protective effects of combined chromium picolinate (CrPic) and atorvastatin treatment against hyperlipidemia-induced cardiac injury. Seventy-five male albino rats were divided into five groups (15 rats each). Hyperlipidemia was induced by intraperitoneal injection of a single dose of Triton X-100 (300 mg/kg body weight (b.w) (group ІІ). Treatment of hyperlipidemic rats was induced by daily administration of CrPic at a dose of 200 µg/kg b.w/day (group ІІІ), atorvastatin at a dose of 10 mg/kg/day (group IV), and combined treatment with both (group V) by gavage for 7 days. At the end of experiment, serum and heart tissues were obtained. Hyperlipidemia was confirmed by histopathology of heart tissues, marked serum dyslipidemia, increased atherogenic indices, and values of ischemia-modified albumin. In addition to increased values of proprotein convertase subtilisin/kexin type 9, activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme and high relative expression levels of pentraxin-3 were observed. However, paraoxonase-1 activity was markedly decreased in the hyperlipidemic group. Significant improvement in all assessed parameters was observed in the rat group treated with both CrPic and atorvastatin. It can be concluded that combined CrPic and atorvastatin treatments had synergistic cardioprotective effects against hyperlipidemia which may be through modulating atherosclerosis as well as cardiac and aortic damage and/or activation of anti-inflammatory and anti-oxidant pathways, thus reversing endothelial dysfunction.


Assuntos
Atorvastatina/agonistas , Cromo/uso terapêutico , Suplementos Nutricionais , Modelos Animais de Doenças , Interações Alimento-Droga , Hiperlipidemias/dietoterapia , Hipolipemiantes/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Atorvastatina/uso terapêutico , Biomarcadores/sangue , Biomarcadores/metabolismo , Proteína C-Reativa/agonistas , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Cardiotônicos/agonistas , Cardiotônicos/uso terapêutico , Cromo/agonistas , Terapia Combinada , Regulação da Expressão Gênica/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Hipolipemiantes/química , Lipoproteínas LDL/sangue , Masculino , Octoxinol , Ácidos Picolínicos/administração & dosagem , Distribuição Aleatória , Ratos Sprague-Dawley , Albumina Sérica Humana , Componente Amiloide P Sérico/agonistas , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo
2.
Acta Biomater ; 36: 286-95, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26996376

RESUMO

UNLABELLED: We recently demonstrated that the effectiveness of tobramycin (Tob), an aminoglycoside, against antibiotic-tolerant persister cells of Pseudomonas aeruginosa can be enhanced by electrochemical factors generated from direct currents (DC). Supplementation of Ni(II), Cr(III) and Fe(II) during carbon-mediated DC treatment revealed that these metal cations promote killing of persister cells in the presence of tobramycin, which led to our hypothesis that specific interactions between Tob and some metal ions contribute to the synergistic killing of persister cells. In this study, the interactions between selected metal cations and Tob were investigated using (1)H-(13)C HSQC NMR. Increase in the concentration of Cr(III) (in the form of [CrCl2(H2O)4](+)) in solutions containing Tob was found to shift the HSQC NMR peaks of Tob to new positions, suggesting the formation of a Cr(III)-Tob complex. Crystal field effects and electrochemical properties of the complex were further studied using UV-visible spectroscopy and cyclic voltammetry, which led to the finding that the Cr(III)-Tob complex has increased affinity with negatively charged nucleic acids. These findings are helpful for understanding the mechanism of electrochemical control of bacterial cells and for developing more effective antimicrobial therapies based on aminoglycosides and electrochemical species released from various metallic biomaterials. STATEMENT OF SIGNIFICANCE: Medical device associated infections present a major challenge to healthcare and the quality of life of affected individuals. This problem is further exacerbated by the emergence of multidrug resistant pathogens. Thus, alternative methods for microbial control are urgently needed. Recently, we reported synergy between tobramycin and low-level electrochemical currents generated using stainless steel electrodes in killing bacterial persister cells, a dormant population with high-level intrinsic tolerance to antibiotics. In this article, we describe how electrically-induced interaction between aminoglycosides and certain metal cations enhance the potency of tobramycin in bacterial killing. The findings will help design new methods for controlling infections through electrochemical disruption of cellular function and associated drug resistance.


Assuntos
Cromo/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Tobramicina/farmacologia , Cromo/agonistas , Sinergismo Farmacológico , Tobramicina/química
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