Modulatory Effect of 2-(4-Hydroxyphenyl)amino-1,4-naphthoquinone on Endothelial Vasodilation in Rat Aorta

The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione) at various doses modulate this process in a variety of ways. In this study, Q7, a 2-phenylamino-1,4-naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells. Q7 reduced nitric oxide (NO) levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl2 was added to a calcium-free medium but did not affect the influx of calcium from extracellular space. Q7 increased the vasoconstriction to BaCl2 (10-3 M), an inward rectifying K+ channels blocker, and blocked the vasodilation to KCl (10-2 M) in aortic rings precontracted with BaCl2. This was recovered with sodium nitroprusside (10-8 M), a NO donor. In conclusion, Q7 induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K+ channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation

UHPLC-MS Phenolic Fingerprinting, Aorta Endothelium Relaxation Effect, Antioxidant, and Enzyme Inhibition Activities of Azara dentata Ruiz & Pav Berries

Azara dentata Ruiz & Pav. is a small Chilean native plant from Patagonia, a producer of small white reddish berries. For the first time, the proximal analysis of the fruits, phenolic fingerprinting, the antioxidant activity, and the enzymatic inhibition and relaxation effects in rat aorta induced by the ethanolic extract of these fruits were investigated. The proximal composition and the mineral (Ca: 2434 ± 40 mg/kg; Mg: 702 ± 13 mg/kg; Fe: 117.1 ± 1.6 mg/kg; Zn: 16.1 ± 0.4 mg/kg) and heavy metal (As: 121 ± 11 µg/kg; Cd: 152 ± 5 µg/kg; Hg: 7.7 ± 1.3 µg/kg; Pb 294 ± 4 µg/kg) contents were analyzed. Anthocyanins, flavonoids, phenolic acids, and coumarins were identified using UHPLC-PDA-QTOF-MS. The ethanolic extracts showed a total phenolic content of 23.50 ± 0.93 mg GAE/g extract. In addition, the antioxidant activity was assessed using both DPPH and TEAC (28.64 ± 1.87 and 34.72 ± 2.33 mg Trolox/g of dry fruit, respectively), FRAP (25.32 ± 0.23 mg Trolox equivalent/g dry fruit), and ORAC (64.95 ± 1.23 mg Trolox equivalents/g dry fruit). The inhibition of enzymatic activities (acetylcholinesterase IC50: 2.87 + 0.23 µg extract/mL, butyrylcholinesterase IC50: 6.73 + 0.07 µg extract/mL, amylase IC50: 5.6 ± 0.0 µg extract/mL, lipase IC50: 30.8 ± 0.0 µg extract/mL, and tyrosinase IC50: 9.25 ± 0.15 µg extract/mL) was also assessed. The extract showed 50–60% relaxation in rat aorta (intact), mediated thorough the release of endothelial nitric oxide. Our results suggest that A. dentata is a good source of compounds with the capacity to inhibit important enzymes, can be hypotensive, and can thus have good potentiality as supplements in the amelioration of neurodegenerative diseases and could also have potential to be used to develop new functional foods. The study highlights the benefits of these neglected small fruits and could boost their consumption.Fil: Cuesta Ramos, Lucia. Universidad de Valencia; EspañaFil: Palacios, Javier. Universidad Arturo Prat (unap);Fil: Barrientos, Ruth E.. Universidad Austral de Chile; ChileFil: Gómez Pelaytay, Jessica Belén. Universidad Nacional de San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Castagnini, Juan Manuel. Universidad de Valencia; EspañaFil: Barba, Francisco J.. Universidad de Valencia; EspañaFil: Tapia, Alejandro. Universidad Nacional de San Juan; ArgentinaFil: Paredes, Adrián. Universidad de Antofagasta (uantof);Fil: Cifuentes, Fredi. Universidad de Antofagasta (uantof);Fil: Simirgiotis, Mario J.. Universidad Austral de Chile; Chil

Polyphenolic Composition and Hypotensive Effects of Parastrephia quadrangularis (Meyen) Cabrera in Rat

Parastrephia quadrangularis (Pq), commonly called “Tola”, is widely used in folk medicine in the Andes, including for altitude sickness. In this study, polyphenolic composition was determined, and hypotensive effects were measured; the ethnopharmacological use as hypotensive was related to the presence of phenolic compounds. For this purpose, male Sprague-Dawley rats (6 to 8 weeks of age, 160 to 190 g) were fed Pq extract (10 to 40 mg/kg) for 10 days through gavage. Blood pressures and heart rate were significantly (p < 0.01) reduced in normotensive rats receiving Pq extract (40 mg/kg body weight). Pq extract induced a negative inotropic effect, and endothelium-dependent vasodilation mediated by nitric oxide (NO). Furthermore, preincubation with Pq extract significantly decreased the cytosolic calcium on vascular smooth muscle cells A7r5 in response to L-phenylephrine (PE). Seven metabolites were isolated from the Pq extract, but three flavonoids (10−4 M) showed similar vasodilation to the extract in intact rat aorta as follows: 5,3′,4′-trihydroxy-7-methoxyflavanone (2); 3,5,4′-trihydroxy-7,8,3′-trimethoxyflavone (6); and 5,4′-dihydroxy-3,7,8,3′-tetramethoxyflavone (7). The Pq extract and compounds 2 and 7 significantly (p < 0.05) reduced the contraction to Bay K8644 (10 nM, an agonist of CaV1.2 channels). Administration of Pq decreased cardiac contractility and increased endothelium-dependent and -independent vasodilation

Alteracoes comportamentais induzidas pelo tratamento pre-natal com diazepam e ro 15-1788

BV UNIFESP: Teses e dissertaçõe

Efeitos sobre a prole do tratamento com diazepam ou RO 15-1788 durante a gestacao

BV UNIFESP: Teses e dissertaçõe

Relationship between the Ergonomic State of the Classroom Measured in Energy Units and the Well-being of Students Observed by Non-invasive Instrumentation

AbstractThis work aims to measure the ergonomic level of a classroom by means of the quantification of two readily measurable variables. The central hypothesis is that the greater the ergonomic level of the classroom, the higher the well-being of the students and, consequently, the less of total environmental adjustments that must be done to achieve a comfortable situation. Previous research put forward that when human beings are faced with non-pleasing environments, immediately emerges a state of restlessness, which is behaviorally manifested by postural changes and surrounding observation assessing both the sources of discomfort and the potential resources to avoid them. This fact is mainly attested by the movements of the head, the part of the body that concentrates all the sensory system, and the rest of the body. Regarding that the well-being experienced by a student in a specific learning environment is reflected in the body of the individual, we choose to measure these movements as a proxy variable of the ergonomic level of the classroom. A second variable can be measured during the first few minutes of the class by recording the distance displacement of objects and the modification of other aspects of the classroom made by the students to get a better condition to be in it. We choose the net amount of energy required to do these changes as another proxy variable to estimate the ergonomics of the classroom. This second variable is measured once the students are free to make adjustments in the classroom quantifying the energy used for this purpose. These observations are plotted on a Cartesian plane revealing a clear correlation between energy and movements, confirming that both variables are quantitative indicators of the ergonomic state of the classroom, the main artificial ecosystem of learning

8-Oxo-9-Dihydromakomakine Isolated from <i>Aristotelia chilensis</i> Induces Vasodilation in Rat Aorta: Role of the Extracellular Calcium Influx

8-Oxo-9-dihydromakomakine is a tetracyclic indole alkaloid extracted from leaves of the Chilean tree Aristotelia chilensis. The present study investigated the effects of this alkaloid on vascular response in tissues isolated from aortic segments obtained from normotensive rats. Our results showed that 8-oxo-9-dihydromakomakine induced a dose-dependent relaxation of aortic rings pre-contracted with phenylephrine (PE; 10&#8722;6 M). The vasorelaxation induced by 8-oxo-9-dihydromakomakine in rat aortic rings is independent of endothelium. The pre-incubation of aortic rings with 8-oxo-9-dehydromakomakine (10&#8722;4 M) significantly reduced the contractile response to KCl (p &lt; 0.001) more than PE (p &lt; 0.05). The highest dose of 8-oxo-9-dehydromakomakine (10&#8722;4 M) drastically reduced the contraction to KCl (6&#183;10&#8722;2 M), but after that, PE (10&#8722;6 M) caused contraction (p &lt; 0.05) in the same aortic rings. The addition of 8-oxo-9-dihydromakomakine (10&#8722;5 M) decreased the contractile response to tetraethylammonium (a voltage-dependent potassium channels blocker; TEA; 5 &#215; 10&#8722;3 M; p &lt; 0.01) and BaCl2 (a non-selective inward rectifier potassium channel blocker; 5 &#215; 10&#8722;3 M; p &lt; 0.001) in rat aorta. 8-oxo-9-dihydromakomakine (10&#8722;5 M) decreased the contractile response to PE in rat aorta in the presence or absence of ouabain (an inhibitor of Na,K-ATPase; 10&#8722;3 M; p &lt; 0.05). These results could indicate that 8-oxo-9-dihydromakomakine partially reduces plasma membrane depolarization-induced contraction. In aortic rings depolarized by PE, 8-oxo-9-dihydromakomakine inhibited the contraction induced by the influx of extracellular Ca2+ in a Ca2+ free solution (p &lt; 0.01). 8-oxo-9-dihydromakomakine reduced the contractile response to agonists of voltage-dependent calcium channels type L (Bay K6844; 10&#8722;8 M; p &lt; 0.01), likely decreasing the influx of extracellular Ca2+ through the voltage-dependent calcium channels. This study provides the first qualitative analysis indicating that traditional folk medicine Aristotelia chilensis may be protective in the treatment of cardiovascular pathologies