scholarly journals ZnO Nanoparticles Induce Dyslipidemia and Atherosclerotic Lesions Leading to Changes in Vascular Contractility and Cannabinoid Receptors Expression as Well as Increased Blood Pressure

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2319
Author(s):  
Adriana Ceballos-Gutiérrez ◽  
Alejandrina Rodríguez-Hernández ◽  
María del Rosario Álvarez-Valadez ◽  
Saraí Limón-Miranda ◽  
Felipa Andrade ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Zno Nanoparticles ◽  
Cannabinoid Receptors ◽  
Therapeutic Potential ◽  
Contractile Activity ◽  
Cardiovascular Effects ◽  
In Vitro Assays ◽  
Wall Structure ◽  
Vascular Contractility

ZnO nanoparticles (ZnONPs) have been shown to have therapeutic potential in some diseases such as diabetes and cancer. However, concentration-dependent adverse effects have also been reported. Studies which evaluate the effects of ZnONPs on the cardiovascular system are scarce. This study aimed to evaluate the cardiovascular effects of a low dose of ZnONPs administered chronically in healthy rats. Changes in dyslipidemia biomarkers, blood pressure, aortic wall structure, vascular contractility, and expression of cannabinoid receptors in the aorta wall were evaluated. Healthy rats were divided into two groups: control or treated (one, two, and three months). The treated rats received an oral dose of 10 mg/kg/day. The results showed that treatment with ZnONPs induced dyslipidemia from the first month, increasing atherosclerosis risk, which was confirmed by presence of atherosclerotic alterations revealed by aorta histological analysis. In in vitro assays, ZnONPs modified the aorta contractile activity in response to the activation of cannabinoid receptors (CB1 and CB2). The expression of CB1 and CB2 was modified as well. Moreover, ZnONPs elicited an increase in blood pressure. In conclusion, long-time oral administration of ZnONPs induce dyslipidemia and atherosclerosis eliciting alterations in aorta contractility, CB1 and CB2 receptors expression, and an increase in blood pressure in healthy rats.

scholarly journals Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3389
Author(s):  
Ishtiaq Ahmed ◽  
Saif Ur Rehman ◽  
Shiva Shahmohamadnejad ◽  
Muhammad Anjum Zia ◽  
Muhammad Ahmad ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Autoimmune Disorders ◽  
Specific Receptors ◽  
Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

scholarly journals Genetic deletion of trkB.T1 increases neuromuscular function

2012 ◽  
Vol 302 (1) ◽  
pp. C141-C153 ◽  
Author(s):  
Susan G. Dorsey ◽  
Richard M. Lovering ◽  
Cynthia L. Renn ◽  
Carmen C. Leitch ◽  
Xinyue Liu ◽  
...  
Keyword(s):  
Calcium Release ◽  
Contractile Activity ◽  
Muscle Tension ◽  
Neuromuscular Synapse ◽  
Neuromuscular Function ◽  
In Vitro Assays ◽  
Tyrosine Kinase Receptor ◽  
Akt Activation

Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB ( trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1 −/− animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function.

The α2-isoform of Na-K-ATPase mediates ouabain-induced hypertension in mice and increased vascular contractility in vitro

2005 ◽  
Vol 288 (2) ◽  
pp. H477-H485 ◽  
Author(s):  
Iva Dostanic ◽  
Richard J. Paul ◽  
John N. Lorenz ◽  
Steven Theriault ◽  
James W. Van Huysse ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Left Ventricular ◽  
Genetically Engineered ◽  
Wild Type ◽  
Vascular Contractility ◽  
Genetically Engineered Mice ◽  
Basal Tone ◽  
Induced Hypertension ◽  
Spontaneous Contractions

Although ouabain is known to induce hypertension, the mechanism of how this cardiac glycoside affects blood pressure is uncertain. The present study demonstrates that the α2-isoform of the Na-K-ATPase mediates the pressor effects of ouabain in mice. To accomplish this, we analyzed the effect of ouabain on blood pressure in wild-type mice, where the α2-isoform is sensitive to ouabain, and genetically engineered mice expressing a ouabain-insensitive α2-isoform of the Na-K-ATPase. Thus differences in the response to ouabain between these two genotypes can only be attributed to the α2-isoform of Na-K-ATPase. As the α1-isoform is naturally resistant to ouabain in rodents, it will not be inhibited by ouabain in either genotype. Whereas prolonged administration of ouabain increased levels of ouabain in serum from both wild-type and targeted animals, hypertension developed only in wild-type mice. In addition, bolus intravenous infusion of ouabain increased the systolic, mean arterial, and left ventricular blood pressure in only wild-type anesthetized mice. In vitro, ouabain increased vascular tone and thereby phenylephrine-induced contraction of the aorta in intact and endothelium-denuded wild-type mice but in α2-resistant mice. Ouabain also increased the magnitude of the spontaneous contractions of portal vein and the basal tone of the intact aorta from only wild-type mice. The increase in aortic basal tone was dependent on the presence of endothelium. Our studies also demonstrate that the α2-isoform of Na-K-ATPase mediates the ouabain-induced increase in vascular contractility. This could play a role in the development and maintenance of ouabain-induced hypertension.

BPP-5a produces a potent and long-lasting NO-dependent antihypertensive effect

2011 ◽  
Vol 5 (6) ◽  
pp. 281-295 ◽  
Author(s):  
Danielle Ianzer ◽  
Carlos Henrique Xavier ◽  
Fabiana Costa Fraga ◽  
Roberto Queiroga Lautner ◽  
Juliano Rodrigo Guerreiro ◽  
...  
Keyword(s):  
Ace Inhibitor ◽  
Antihypertensive Effect ◽  
Ex Vivo ◽  
Cardiovascular Effects ◽  
Ace Inhibition ◽  
In Vitro Assays ◽  
Spontaneously Hypertensive ◽  
Angiotensin I Converting Enzyme ◽  
Animal Venoms

Background: The bradykinin potentiating peptides (BPPs) are oligopeptides found in different animal venoms. BPPs isolated from Bothrops jararaca venom were the first natural inhibitors described for somatic angiotensin I-converting enzyme (ACE). They were used in the structural modeling for captopril development, a classical ACE inhibitor widely used to treat human hypertension. Methods: We evaluated the effect of BPP-5a on cardiovascular parameters of conscious Wistar (WTs) and spontaneously hypertensive rats (SHRs). Results: In SHR, BPP-5a showed potent cardiovascular effects, at doses ranging from 0.47 to 710 nmol/kg. The maximal changes in mean arterial pressure (MAP) and heart rate (HR) were found at the dose of 2.37 nmol/kg (Δ MAP: −38 ± 4 mmHg, p < 0.01; Δ HR: −71 ± 17 bpm, p < 0.05). Reductions in MAP and HR occurred throughout 6 hours of post-injection period. In contrast to active site-directed ACE inhibitors, no ACE inhibition, evaluated by the Ang I pressor effect, or bradykinin potentiation was observed during the antihypertensive effect of the pentapeptide. In vitro assays showed no effects of BPP-5a upon argininosuccinate synthetase and B1, B2, AT1, AT2 or Mas receptors. Ex vivo assays showed that BPP-5a induced endothelium-dependent vasorelaxation in isolated aortic rings of SHRs and WTs. Conclusions: Although the BPP-5a is considered an ACE inhibitor, our results indicate that its antihypertensive effect is exerted via a unique target, a nitric-oxide-dependent mechanism.

scholarly journals Vegetal diamine oxidase alleviates histamine-induced contraction of colonic muscles

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Armelle Tchoumi Neree ◽  
Rodolphe Soret ◽  
Lucia Marcocci ◽  
Paola Pietrangeli ◽  
Nicolas Pilon ◽  
...  
Keyword(s):  
Diamine Oxidase ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Active Form ◽  
Distal Colon ◽  
Biologically Active ◽  
In Vitro Assays ◽  
Histaminase Activity ◽  
Irritable Bowel

AbstractExcess of histamine in gut lumen generates a pronounced gastrointestinal discomfort, which may include diarrhea and peristalsis dysfunctions. Deleterious effects of histamine can be alleviated with antihistamine drugs targeting histamine receptors. However, many antihistamine agents come with various undesirable side effects. Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. Mammalian intestinal mucosa contains an endogenous DAO, yet possessing lower activity compared to that of vDAO preparation. Moreover, in several pathological conditions such as inflammatory bowel disease and irritable bowel syndrome, this endogenous DAO enzyme can be lost or inactivated. Here, we tested the therapeutic potential of vDAO by focusing on the well-known effect of histamine on gut motility. Using ex vivo and in vitro assays, we found that vDAO is more potent than commercial anti-histamine drugs at inhibiting histamine-induced contraction of murine distal colon muscles. We also identified pyridoxal 5′-phosphate (the biologically active form of vitamin B6) as an effective enhancer of vDAO antispasmodic activity. Furthermore, we discovered that rectally administered vDAO can be retained on gut mucosa and remain active. These observations make administration of vDAO in the gut lumen a valid alternative treatment for histamine-induced intestinal dysfunctions.

Phytochemical and Biological Activities of five Turanecio Hamzaoglu (Asteraceae) Species from Turkey

2017 ◽  
Vol 13 (1) ◽  
pp. 49-55
Author(s):  
Sevil Albayrak ◽  
Ahmet Aksoy ◽  
Abit Yasar ◽  
Lutfiye Yurtseven ◽  
Umit Budak
Keyword(s):  
Therapeutic Potential ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Natural Antioxidants ◽  
Antibacterial Activities ◽  
Antimicrobial Activities ◽  
In Vitro Assays ◽  
Methanolic Extracts ◽  
Promising Source

Objectives: In vitro biological activities of methanolic extracts of five Turanecio species have been studied. Materials and Methods: The phenolic compositions of the extracts were evaluated by the Folin- Ciocalteu assay and by HPLC analysis. Antioxidant activities were determined with two in vitro assays namely, DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assay and phosphomolybdenum assay. The antimicrobial activities of the extracts were evaluated against 13 microorganisms. Results: T. hypochionaeus var. hypochionaeus was showed the highest DPPH inhibition with 88.84% at 100 μg·mL-1. All of the extracts were exerted high total antioxidant activities 128.00- 243.13 mg AAE g-1) and seem to be a promising source of natural antioxidants. The phenolic contents in the extracts varied from 26.17 to 60.99 mg·g-1 as gallic acid equivalent. Chlorogenic acid, caffeic acid and p- coumaric acid were the predominant constituents. The methanolic extracts revealed promising antibacterial activities against most bacteria. No activity was recorded against yeasts tested. Conclusion: The polyphenolic constituents appear to be responsible, at least in part, for the extract’s activities. The present study confirms that tested Turanecio species contains significant source of phenolics have antioxidant and antimicrobial activities and may have therapeutic potential.

scholarly journals Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure

2006 ◽  
Vol 188 (3) ◽  
pp. 435-442 ◽  
Author(s):  
P W F Hadoke ◽  
R S Lindsay ◽  
J R Seckl ◽  
B R Walker ◽  
C J Kenyon
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Adult Female ◽  
Vascular Function ◽  
Mesenteric Arteries ◽  
Female Rats ◽  
Control Group ◽  
Pregnant Rats ◽  
Vascular Contractility

Excessive exposure to glucocorticoids during gestation reduces birth weight and induces permanent hypertension in adulthood. The mechanisms underlying this programmed elevation of blood pressure have not been established. We hypothesised that prenatal glucocorticoid exposure may lead to vascular dysfunction in adulthood. Pregnant rats received dexamethasone (Dex) (100 μg/kg, s.c.) or vehicle (control) daily throughout pregnancy. Blood pressure was elevated (students t-test, unpaired; P < 0.05) in adult female offspring (aged 12–16 weeks) of Dex-treated mothers (148.0 ± 3.6 mmHg, n=10) compared with the control group (138.0 ± 2.5 mmHg, n=8). Vascular responsiveness in aortae and mesenteric arteries was differentially affected by prenatal Dex: aortae were less responsive to angiotensin II, whereas mesenteric arteries were more responsive to norepinephrine, vasopressin and potassium (mesenteric arteries respond poorly to angiotensin II in vitro). Acetylcholine-mediated, endothelium-dependent relaxation was similar in both groups. Prenatal exposure to Dex had no effect on blood pressure or aldosterone response to acute (15 min, i.v.) infusion of angiotensin II (75 ng/kg per min). In contrast, chronic (2-week, s.c.) infusion of angiotensin II (100 ng/kg per min) produced a greater elevation (P < 0.05) of blood pressure in Dex-treated rats (150.0 ± 3.6 mmHg) than in controls (135.3 ± 5.4 mmHg), and aldosterone levels were higher in Dex-treated animals. There was no angiotensin II-induced medial hypertrophy/hyperplasia in mesenteric arteries from Dex-treated rats. These results indicate that vascular function is altered in a region-specific manner in rats with glucocorticoid-programmed hypertension. Despite a striking increase in mesenteric artery contraction in Dex-treated rats, in vivo studies suggest that abnormalities of the renin-angiotensin-aldosterone system, rather than enhanced vascular contractility, may be responsible for the elevation of blood pressure in these animals.

Abstract P183: Chemokine-like Receptor 1 Mediates the Vasoconstrictor Actions of Chemerin in vitro and in vivo

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Amanda Kennedy ◽  
Peiran Yang ◽  
Cai Read ◽  
Rhoda Kuc ◽  
Janet Maguire ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Therapeutic Potential ◽  
Plasma Concentrations ◽  
Resistance Arteries ◽  
Resistance Vessels ◽  
Increased Risk ◽  
First Time

Hypertensive patients have significantly higher plasma concentrations of the adipokine chemerin compared with healthy controls, and levels of chemerin positively correlate with systolic and diastolic blood pressure. Chemerin activates chemokine-like receptor 1 (CMKLR1 or ChemR23) but it also activates the ‘orphan’ G protein-coupled receptor 1 (GPR1) which has been linked with hypertension. It is therefore crucial to determine whether one or both of these receptors mediate the constrictor actions of chemerin in the vasculature in order to identify a potential new therapeutic target for the treatment of hypertension. Using immunohistochemistry and molecular biology, we localized chemerin to the endothelium, smooth muscle and adventitia, and CMKLR1 and GPR1 to the smooth muscle in human conduit and resistance vessels. Chemerin activated β-arrestin via heterologously expressed receptors GPR1 (pD 2 =9.30±0.05) and CMKLR1 (pD 2 =9.23±0.03) with comparable potency. CCX832, a small molecule antagonist, was fully characterized as highly selective for CMKLR1, with no effect on GPR1 in binding or cell-based functional assays. The C-terminal fragment of chemerin, C9 (chemerin149-157) contracted human saphenous vein (pD 2 =7.30±0.31) and resistance arteries (pD 2 =6.23±0.16), and caused a significant increase in blood pressure in rats in vivo (0.2 μmol, 9.1±1.0 mmHg). These actions were blocked by CCX832, confirming for the first time that a single chemerin receptor, CMKLR1, mediates the constrictor response in humans and in vivo. Our data suggest that chemerin activation of CMKLR1 may contribute to elevated blood pressure; this in combination with the known roles of chemerin in metabolic syndrome and diabetes, could lead to increased risk of cardiovascular disease. This study provides proof of principle that the therapeutic potential of selective CMKLR1 antagonists should be explored.

scholarly journals Evaluation of Leishmania infantum 30x biotherapy effects in the prevention and treatment of visceral leishmaniasis: in vivo and in vitro studies

2021 ◽  
Vol 15 (4) ◽  
pp. 26-29
Author(s):  
Ana Paula Bacellar Cajueiro ◽  
Gleyce Moreno Barbosa ◽  
Fortune Homsani ◽  
Ana Paula dos Santos Matos ◽  
Igor Almeida Rodrigues ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Therapeutic Potential ◽  
Public Health Problem ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Serum Samples ◽  
Hydropic Degeneration ◽  
No Release

Background: Leishmaniasis is a serious public health problem especially in developing countries [1]. The therapeutic potential of biotherapics against several microorganism has been described in vitro [2,3] and in vivo studies [4,5,6,7,8,9]. Considering the resistance of leishmaniasis to conventional treatment as well as previous studies with biotherapic, we evaluated the effects of Leishmania infantum 30x (BioLi30x) biotherapy. Aim: evaluate the antileishmanial effects of BioLi30x in in vivo and in vitro models. Methodology: The in vivo experiments were performed using BALB/c mice (n=138), divided into 8 groups: G1-healthy, G2-infected with L. infantum, G3-BioLi30x pre-treated, G4-BioLi30x pre/post-treated, G5-BioLi30x post-treated, G6-H2O30x post-treated, G7-Antimonium crudum 30x post-treated and G8-Glucantime® post-treated. After 49 days of treatment, the animals were submitted to euthanasia (ethical approval ECUA/UFRJ/066/14). Liver and spleen histological changes were evaluated, and serum samples were aliquoted and storage at -20°C for cytokine assays. The in vitro assays were performed using RAW 264.7 macrophages treated with BioLi30x and infected with L. infantum. The morphological aspects were evaluated by scanning electron microscopy (SEM), and the nitric oxide (NO) release was quantified in the supernatant of infected macrophages. Results: The histological analysis from 4 independent experiments showed livers with normal appearance (G1); periportal chronic hepatitis (G2,G4,G5,G8); discreet (G3,G7), moderate (G4,G5,G6), and severe (G2,G8) vacuolar hydropic degeneration; congestion and neutrophilic inflammation (G2,G4,G5,G6,G8), and possible amastigotes within macrophages (G2-G8). Spleens presented healthy appearance only in G1. All treated animals presented histological alterations, with different lesions severity, which involved spleen pulp hyperplasia with moderate disruption (G2,G8), as well as megakaryocytes and macrophages proliferation (G2- G8). SEM analyses showed BioLi30x treatments induced significant protozoan morphology alterations when compared to H2O30x. Besides, a 19% increase in the NO release was detected in RAW supernatants, when compared to H2O30x. Conclusions: BioLi30x and Antimonium crudum 30x modified the infection animal process, involving several cellular mechanisms as well as different histological damage. The in vitro experiments will be repeated in order to confirm these preliminary results.

scholarly journals Confirmation of Cage Effect and Prebiotic Production Potential of a β-Mannanase, with SBM as Substrate Using Microscopy and Wet Chemistry

2021 ◽  
Vol 13 (2) ◽  
pp. 23
Author(s):  
L. M. Gomez-Osorio ◽  
Hwa Gyun Oh ◽  
Jung Jin Lee
Keyword(s):  
Cell Wall ◽  
Cell Walls ◽  
Plant Cell Wall ◽  
Degree Of Polymerization ◽  
In Vitro Assays ◽  
Wall Structure ◽  
Specific Substrate ◽  
Mannan Oligosaccharides

In vitro assays were carried out to investigate the solubilization of cell walls and generation of mannan oligosaccharides of a b-mannanase-containing commercial product on SBM. Using commercial dosages of the b-mannanase (500 g per ton of feed) cell wall degradation of mannan in SBM cell walls was visualized and an increase in reducing ends (0.12&plusmn;0.02 mg/mL) and the generation of mannan oligosaccharides of degree of polymerization 2 and 4 (22.9&plusmn;3.2 mg/L and 398.8&plusmn;25.4 mg/L) were also measured using HPLC. Mannan, which is H-bonded to cellulose and xyloglucan, was solubilized using a single monocomponent enzyme, allowing for visualization of the disintegration of the entire SBM cell wall structure. This work is the first of its kind using strictly commercial dosage levels of enzyme for evaluating efficacy of the same microscopically. These data confirm the hypothesis that there most likely is a need for only a single relevant NSP enzyme targeting its specific substrate, independent of the concentration of the latter within the complex polysaccharide matrix in the plant cell wall to experience the beneficial effects of the enzyme both in vitro and in vivo. An analogy to compare our data would be destruction of the foundation (mannan) of a building or a bridge (soybean cell wall) which would inevitably lead to dismantling or demolition the entire building or bridge.

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