RESUMO
Early diagnosis and efficient treatment of preeclampsia remains a medical challenge and etiological factors converge in a deficient placentation that triggers oxidative stress. There is evidence that statins show antioxidant effects that can improve endothelial function without adverse perinatal effects. We aimed to compare early vs. late pravastatin treatment on the oxidative stress and cardiovascular features of an experimental model of preeclampsia. Female Wistar rats were randomly divided into preeclampsia phenotype rats (PEP) developed by sub renal aortic coarctation (SRAC) and healthy pregnant rats (C). Each group received pravastatin (5 mg/Kg) p.o. either for one week before and during the first week or during the last two weeks of gestation. Blood pressure was determined using the plethysmographic method. Phenylephrine (Phe)-induced contractility was evaluated in isolated thoracic and abdominal aortic rings with or without endothelium. Blood samples were obtained to determine anion superoxide concentration as indicator of NADPH activity. Two-way ANOVA and Bonferroni post hoc tests were used to define statistical significance. Early or late pravastatin treatment decreased hypertension of PEP animals but did not change BP of the healthy pregnant group. Thoracic and abdominal aorta from PEP rats showed increased contractility that was reverted by pravastatin early treatment in endothelium intact rings. Pravastatin did not significantly change contractility neither in the thoracic nor in the abdominal aorta segments from healthy pregnant control rats (C), and decrease anion superoxide concentration by NADPH activity. We conclude pravastatin can improve both blood pressure and endothelium-dependent Phe-induced contractility in an experimental model of preeclampsia by reducing oxidative stress.
Assuntos
Pravastatina , Pré-Eclâmpsia , Gravidez , Humanos , Ratos , Feminino , Animais , Pravastatina/farmacologia , Pravastatina/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Superóxidos/farmacologia , NADP/farmacologia , Ratos Wistar , Estresse Oxidativo , Fenilefrina/farmacologia , Endotélio VascularRESUMO
INTRODUCTION: Obesity during pregnancy can contribute to hypertensive complications through changes in glucose utilization. We investigated the impact of vascular glucose uptake, GLUT4 density, and endothelium on agonist-induced vasoconstriction in the aortas of overweight pregnant rats. METHODS: Isolated aortic rings with or without endothelium from pregnant or nonpregnant rats fed a standard (SD) or hypercaloric diet (HD) were contracted with phenylephrine or serotonin (10-9 to 10-4
Assuntos
Sobrepeso , Gravidez , Vasoconstrição , Animais , Feminino , Gravidez/metabolismo , Ratos , Aorta , Glicemia/metabolismo , Endotélio Vascular , Sobrepeso/metabolismo , Fenilefrina/farmacologia , Fenilefrina/metabolismo , Serotonina/farmacologia , Serotonina/metabolismoRESUMO
BACKGROUND: Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and Conclusion: Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Fígado/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Fitosteróis/uso terapêutico , Triterpenos/uso terapêutico , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/prevenção & controle , Humanos , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/prevenção & controle , Síndrome Metabólica/metabolismo , Síndrome Metabólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fitosteróis/química , Fitosteróis/farmacologia , Triterpenos/química , Triterpenos/farmacologiaRESUMO
AIMS: Considering phycobiliproteins of Spirulina maxima has shown a wide margin of security in pregnant and non-pregnant animals as well as antioxidant properties, present study aimed to investigate if the cardiovascular and metabolic effects of an experimental model of preeclampsia can be prevented by the administration of this compound. MAIN METHODS: Subrenal aortic coarctation (SRAC) practiced to female Wistar rats of 8â¯weeks of age. Animals were divided randomly to conform non-pregnant and pregnant groups and pregnant with SRAC showed fetoplacental ischemia and were considered preeclamptic (PE). Groups were treated with saline solution (control group) or phycobiliproteins solution (100â¯mg/kg/day ig) for the last 7, 14 or 20â¯days of pregnancy. KEY FINDINGS: PE animals showed increased systolic blood pressure, weight gain, glucose and GTT as well as vascular contractility. Also, PE animals showed decreased SOD, GPx activities while MDA was increased. Phycobiliproteins oral treatment for 3â¯weeks significantly decreased systolic blood pressure and reestablished glucose, weight gain and vascular contractility as well as enzyme activities of PE rats to those of normal pregnant animals. SIGNIFICANCE: Our results show that phycobiliproteins can prevent the damage produced by fetoplacental ischemia and provides evidence of free radical species contribution to the physiopathology of the disease. Also, we conclude phycobiliproteins can be an alternative to reduce preeclampsia manifestations, however, more studies are recommended.
Assuntos
Coartação Aórtica/tratamento farmacológico , Modelos Animais de Doenças , Estresse Oxidativo/efeitos dos fármacos , Ficobiliproteínas/administração & dosagem , Pré-Eclâmpsia/tratamento farmacológico , Spirulina/química , Animais , Coartação Aórtica/patologia , Pressão Sanguínea/efeitos dos fármacos , Feminino , Pré-Eclâmpsia/patologia , Gravidez , Ratos , Ratos WistarRESUMO
To study whether hypercaloric diet-induced obesity deteriorates vascular contractility of rat aorta through functional changes in α1 adrenergic and/or AT1 Angiotensin II receptors. Angiotensin II- or phenylephrine-induced contraction was tested on isolated aorta rings with and without endothelium from female Wistar rats fed for 7 weeks with hypercaloric diet or standard diet. Vascular expression of Angiotensin II Receptor type 1 (AT1R), Angiotensin II Receptor type 2 (AT2R), Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), inducible Nitric Oxide Synthase (iNOS) and endothelial Nitric Oxide Synthase (eNOS), as well as blood pressure, glucose, insulin and angiotensin II blood levels were measured. Diet-induced obesity did not significantly change agonist-induced contractions (Emax and pD2 hypercaloric diet vs standard diet n.s.d.) of both intact (e+) or endothelium free (e-) vessels but significantly decrease both phenylephrine and angiotensin II contraction (Emax p < 0.01 hypercaloric diet vs standard diet) in the presence of both prazosin and losartan but only in endothelium-intact vessels. Diet-induced obesity did not change angiotensin II AT1, AT2 receptor proteins expression but reduced COX-1 and NOS2 ( p < 0.05 vs standard diet). Seven-week hypercaloric diet-induced obesity produces alterations in vascular adrenergic and angiotensin II receptor dynamics that suggest an endothelium-dependent adrenergic/angiotensin II crosstalk. These changes reflect early-stage vascular responses to obesity.
Assuntos
Aorta/metabolismo , Dieta/efeitos adversos , Endotélio Vascular/metabolismo , Obesidade/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Vasoconstrição , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Ingestão de Energia , Feminino , Técnicas In Vitro , Proteínas de Membrana/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Obesidade/etiologia , Obesidade/fisiopatologia , Ratos Wistar , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Receptor Tipo 2 de Angiotensina/metabolismo , Receptores Adrenérgicos alfa 1/efeitos dos fármacos , Transdução de Sinais , Fatores de Tempo , Vasoconstrição/efeitos dos fármacosRESUMO
BACKGROUND: Surgically induced adhesions complicate up to 100% of abdominal surgeries. Food and Drug Administration-approved treatments are generally not only less effective than desired but they also have major contraindications. Oxychlorine species, including chlorine dioxide (ClO2), suppress scar formation in infected wounds without affecting keratinocytes while reducing fibroblast proliferation. The aim of the present study was to evaluate the effect of oxychlorine solutions containing ClO2 on adhesion formation. METHODS: Male Wistar rats were subjected to Buckenmaier model of surgical adhesions and treated with either oxychlorine solutions containing ClO2 (40-150 ppm) or isotonic saline solution. To increase the severity of adhesions, peritonitis was produced by intraperitoneal administration of a diluted nonlethal dose of feces (50 mg/kg). Wound strength of the healed wound was measured to evaluate the effects of oxychlorine solutions. In addition, an oxychlorine solution of lesser efficacy (at 100 ppm) was compared with three available anti-adhesion materials. RESULTS: Reproducibility of the model was validated in 26 rats. Oxychlorine solutions containing ClO2 (40-110 ppm) significantly reduced postsurgical adhesion formation without affecting the strength of the healed wound. Higher concentrations (120 and 150 ppm) had no effect. Fecal peritonitis significantly increased, and solutions with ClO2 at 110 ppm significantly reduced adhesion formation. The effect of the oxychlorine solution was significantly greater than that of Interceed, Guardix, Seprafilm, and isotonic saline solution. CONCLUSIONS: ClO2-containing oxychlorine solutions could be an innovative strategy for the suppression of surgical adhesion formation, with the additional advantage of contributing antiseptic properties.