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Preclinical Research Potassium (K+ ) channels have a key role in the maintenance of smooth muscle tone; a variety of agonists can modify the tone by altering K+ -channel activity. The aim of this study was assess the effects of the phenols, resveratrol, and naringenin on K+ -channels of the vascular smooth muscle. Segments of human umbilical vein (HUV) without endothelium were precontracted using serotonin (100 µM) or 100 mM K+ to derive cumulative concentration-response curves using increasing concentrations of resveratrol or naringenin. K+ -channel inhibitors were added in the bath before resveratrol (1-100 µM) or naringenin (0.01-1 mM) in assess the role of K+ -channels in their effects on HUV precontracted by serotonin. 4-Aminopiridine (4-AP; 1 mM), a nonselective blocker of voltage-dependent, tetraethylammonium (TEA; 1 mM) and barium chloride (1 mM), a nonselective blocker of Ca2+ -dependent and inward rectifier K+ -channels (respectively) induced significant shifts to the right (P < 0.05) of resveratrol. concentration-response curves. The effect of naringenin was antagonized by 4-AP (1 mM). 4-AP-, TEA-, and barium chloride-sensitive K+ -channels are probably involved in the resveratrol vasodilatatory effect, while naringenin seems to affect 4-AP-sensitive K+ -channels. However, other mechanisms of vasodilation induced by polyphenols could not be excluded. Drug Dev Res, 2015. © 2015 Wiley Periodicals, Inc.
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The blood flow from the placenta to the fetus depends on human umbilical vein (HUV) vascular tone. ATP-sensitive K(+) (K(ATP)) channels link the metabolic state of the cell to membrane potential, and their activation in the HUV represents protection against hypoxia. The aims of our study were to assess the effects of resveratrol and naringenin on the HUV and to define the roles of K(ATP) channels in their effects. Serotonin or 100 mM K(+) were used for precontraction of the HUV without endothelium. The cumulative concentration-response curves were obtained by adding increasing concentrations of resveratrol or naringenin. Glibenclamide was used, in order to test the role of K(ATP) channels in its effect. Resveratrol induced more potent vasodilatation of serotonin- and 100 mM K(+)-precontracted HUV than naringenin. Glibenclamide induced significant shift to the right of the concentration-response curves of resveratrol and P1075 (a specific opener of K(ATP) channels). Western blotting showed that HUV expressed protein Kir6.1. Thus, resveratrol and naringenin produce dilatation of HUV. It seems that K(ATP) channels are involved in the relaxation of HUV induced by resveratrol, while naringenin seems to interact with other ion channels. The K(+) channel-independent mechanism(s) of these polyphenols could not be excluded.
Asunto(s)
Flavanonas/farmacología , Canales KATP/metabolismo , Estilbenos/farmacología , Venas Umbilicales/efectos de los fármacos , Vasodilatadores/farmacología , Adulto , Femenino , Gliburida/farmacología , Guanidinas/farmacología , Humanos , Técnicas In Vitro , Piridinas/farmacología , ResveratrolRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is a multisystem reproductive-metabolic disorder and the most common endocrine cause of infertility. The objective of our study was to determine the influence of myo-inositol (MI) on insulin resistance (IR), menstrual cycle regularity, and hyperandrogenism in women suffering from PCOS with normal BMI and diagnosed IR. METHODS: We performed a prospective randomized controlled trial (RCT) that included 60 participants with PCOS who had IR and a normal BMI. Two groups were formed. A group of thirty patients received MI, and thirty patients in the control group received metformin (MET). RESULTS: A statistically significant reduction in the area under the curve (AUC) of insulin values during the oral glucose tolerance test (OGTT) was recorded in both examined groups after the applied therapy with MI and MET. The regularity of the menstrual cycle in both groups was improved in >90% of patients. A statistically significant decrease in androgenic hormones (testosterone, SHBG, free androgen index-FAI, androstenedione) was recorded in both groups and did not differ between the groups. CONCLUSIONS: Both MI and MET can be considered very effective in the regulation of IR, menstrual cycle irregularities, and hyperandrogenism in women with PCOS.
RESUMEN
Background: Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders in women's reproductive period of life. The presence of nonalcoholic fatty liver disease NAFLD, one of the leading causes of chronic liver disease in the Western world, is increased in women with PCOS. This review aims to present current knowledge in epidemiology, pathophysiology, diagnostics, and treatment of NAFLD in PCOS with an emphasis on the molecular basis of development of NAFLD in PCOS women. Methods: Authors investigated the available data on PCOS and NAFLD by a MEDLINE and Pub Med search during the years 1990-2021 using a combination of keywords such as "PCOS", "NAFLD", "steatohepatitis", "insulin resistance", "hyperandrogenaemia", "inflammation", "adipose tissue", and "obesity". Peer-reviewed articles regarding NAFLD and PCOS were included in this manuscript. Additional articles were identified from the references of relevant papers. Results: PCOS and NAFLD are multifactorial diseases, The development of NAFLD in PCOS women is linked to insulin resistance, hyperandrogenemia, obesity, adipose tissue dysfunction, and inflammation. There is the possible role of the gut microbiome, mitochondrial dysfunction, and endocannabinoid system in the maintenance of NAFLD in PCOS women. Conclusions: There is a need for further investigation about the mechanism of the development of NAFLD in PCOS women. New data about the molecular basis of development of NAFLD in PCOS integrated with epidemiological and clinical information could influence the evolution of new diagnostic and therapeutic approaches of NAFLD in PCOS.