RESUMO
INTRODUCTION: The investigations of angiotropic effects of liraglutide are an issue of significant scientific and practical interest. The successful application of liraglutide has been shown in glycemic control in patients with the type 2 diabetes mellitus (DM), but the effect of liraglutide in patients with type 1 DM has not been completely studied yet in clinical practice. Therefore, the present study is aimed to investigate the effect of liraglutide which is agonist of glucagon-like peptide-1 receptors, on microcirculation in white outbred rats with the alloxan-induced diabetes. MATERIALS AND METHODS: The study was performed with 70 white outbred rats, divided into 4 groups: 1) control group (intact animals (Control)); 2) comparison group (diabetes mellitus (DM)) - animals with the alloxan-induced diabetes; 3) experimental group no. 1 (liraglutide low dose (LLD)) - animals with the alloxan-induced diabetes, which were injected by liraglutide at dosage of 0.2â¯mg/kg of animal weight per a day; 4) experimental group no. 2 (liraglutide high dose (LHD)) - animals with the alloxan-induced diabetes, which were injected by liraglutide at dosage of 0.4â¯mg/kg of animal weight per a day. The carbohydrate metabolism disorders, the microcirculation of posterior paw skin, as well as the concentration of catecholamines and markers of endothelial alteration in blood were estimated at the 42nd day of the experiment in the comparison and experimental groups. RESULTS: It was found that the correction of carbohydrate metabolism by liraglutide is succeeded by the normalization of skin perfusion of posterior paw skin of the experimental animals. Recovery of microcirculation is associated with a decrease in vascular tone and stimulation of endothelium-dependent vasodilation, caused by simultaneous decrease of catecholamines, endothelin-1 and asymmetric dimethylarginine (ADMA) concentrations in blood serum. At the same time, the administration of liraglutide on the background of insulin-deficiency results in decrease of endothelial cell alteration markers concentration in blood, such as sE-selectin, syndecan-1, and vascular endothelial growth factor (VEGF). CONCLUSION: Administration of liraglutide leads to the normalization of the carbohydrate metabolism simultaneously with the correction of microcirculation in rats with the absolute insulin deficiency. The demonstrated recovery of microcirculation by liraglutide, which represents an analogue of glucagon-like peptide-1, provides new prospects for its approval as a potential drug for pathogenetic correction of microcirculatory disorders in patients with the type 1 DM.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Incretinas/farmacologia , Insulina/deficiência , Liraglutida/farmacologia , Microcirculação/efeitos dos fármacos , Pele/irrigação sanguínea , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Hemoglobinas Glicadas/metabolismo , Insulina/sangue , Ratos , Fluxo Sanguíneo RegionalRESUMO
The supercritical fluid extraction (SFE) of volatile and fixed oil from milled parsley (Petroselinum crispum L.) seeds, using CO2 as solvent, is presented in this study. Extraction experiments were carried out in two steps: at pressures of (90 or 300) bar and temperature of 40 °C. The first extraction step, performed at 90 bar, produced a volatile fraction mainly formed by apiole (82.1%) and myristicin (11.4%). The volatile oil yield was 2.6% by weight of the charge. The second extraction step, carried out at 300 bar produced a fixed oil at a yield of 0.4% by weight. The most represented fatty acids in P. crispum fixed oil were 18:1 n-12 (49.9%), 18:2 n-6 (18.2%), 18:1 n-9 (11.8%), and 16:0 (7.4%). In particular, the unsaturated fatty acids 18:1 n-12 and 18:1 n-9 averaged 182.2 mg/g and 92.1 mg/g of oil extract, respectively. The quality of the oils extracted by SFE, in terms of its chemical composition, was compared to the oils obtained by hydrodistillation (HD) in a Clevenger apparatus and by solvent extraction (SE) using n-hexane in a Soxhlet apparatus. The antioxidant properties were determined by means of the ABTS assay. The results indicated that the fixed oil possessed low antioxidant activity (EC50 = 0.4 mg/mL) and the volatile oil had no antioxidant activity. The total phenolic content, expressed as concentration of gallic acid (gallic acid equivalent, GAE), of the fixed oil was 1.5 mg/g. The fixed oil found to have inhibitory effects against α-glucosidase, the volatile oil is active on acetylcholinesterase (AChE), tyrosinase, and α-glucosidase. Both samples have weak inhibitory activity on α-amylase and no activity on butyrylcholinesterase (BChE).
Assuntos
Cromatografia com Fluido Supercrítico , Óleos Voláteis , Acetilcolinesterase/análise , Butirilcolinesterase/análise , Dióxido de Carbono/química , Cromatografia com Fluido Supercrítico/métodos , Óleos Voláteis/química , Petroselinum , Óleos de Plantas/química , Sementes/químicaRESUMO
The vascular endothelium performs many functions. It is a key regulator of vascular homeostasis, maintains a balance between vasodilation and vasoconstriction, inhibition and stimulation of smooth muscle cell migration and proliferation, fibrinolysis and thrombosis, and is involved to regulation of platelet adhesion and aggregation. Endothelial dysfunction (ED) plays the critical role in pathogenesis of diabetes mellitus (DM) vascular complications. The purpose of this review was to consider the mechanisms leading to the occurrence of ED in DM. The paper discusses current literature data concerning the role of hyperglycemia, oxidative stress, advanced glycation end products in endothelial alteration. A separate section is devoted to the particularities of the functioning of the antioxidant system and their significance in the development of ED in DM. The analysis of the literature allows to conclude that pathological activation of glucose utilization pathways causes damage of endothelial cells, which is accompanied by disorders of all their basic functions. Metabolic disorders in DM cause a pronounced imbalance of free radical processes and antioxidant defense, accompanied by oxidative stress of endotheliocytes, which contributes to the progression of ED and the development of vascular complications. Many aspects of multicomponent regulatory reactions in the pathogenesis of the development of ED in DM have not been sufficiently studied.
Assuntos
Complicações do Diabetes , Diabetes Mellitus , Hiperglicemia , Células Endoteliais , Endotélio Vascular , HumanosRESUMO
OBJECTIVE: To evaluate serum purine metabolite concentrations in patients affected by fibromyalgia syndrome (FMS) and the relationships between their levels and FM clinical parameters. DESIGN AND METHODS: Serum purine levels were quantified using LC/UV-vis in 22 fibromyalgic females (according to the American College of Rheumatology classification criteria) and 22 healthy females. RESULTS: Significantly higher serum inosine, hypoxanthine and xanthine levels (p<0.001) and significantly lower serum adenosine (p<0.05) were detected in the FMS patients vs healthy controls. Our data show a negative correlation between adenosine and Fibromyalgia Impact Questionnaire (FIQ). CONCLUSIONS: Study results suggest that purines, in particular adenosine and inosine, may be involved in pain transmission in fibromyalgia.