scholarly journals Chronic 5-HT2 receptor blockade unmasks the role of 5-HT1F receptors in the inhibition of rat cardioaccelerator sympathetic outflow

2018 ◽  
Vol 96 (4) ◽  
pp. 328-336 ◽  
Author(s):  
José Ángel García-Pedraza ◽  
Oswaldo Hernández-Abreu ◽  
Mónica García ◽  
Asunción Morán ◽  
Carlos M. Villalón
Keyword(s):  
Drinking Water ◽  
Receptor Antagonist ◽  
Treated Group ◽  
Control Group ◽  
Sympathetic Outflow ◽  
Pharmacological Profile ◽  
Water Control ◽  
Gr 127935 ◽  
Cardiovascular Pathologies

Serotonin (5-hydroxytryptamine; 5-HT) inhibits the rat cardioaccelerator sympathetic outflow by 5-HT1B/1D/5 receptors. Because chronic blockade of sympatho-excitatory 5-HT2 receptors is beneficial in several cardiovascular pathologies, this study investigated whether sarpogrelate (a 5-HT2 receptor antagonist) alters the pharmacological profile of the above sympatho-inhibition. Rats were pretreated for 2 weeks with sarpogrelate in drinking water (30 mg/kg per day; sarpogrelate-treated group) or equivalent volumes of drinking water (control group). Animals were pithed and prepared for spinal stimulation (C7-T1) of the cardioaccelerator sympathetic outflow or for intravenous (i.v.) bolus injections of noradrenaline. Both procedures produced tachycardic responses remaining unaltered after saline. Continuous i.v. infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT receptor agonists 5-carboxamidotryptamine (5-CT; 5-HT1/5A), CP 93,129 (5-HT1B), or PNU 142633 (5-HT1D), but not by indorenate (5-HT1A) in both groups; whereas LY344864 (5-HT1F) mimicked 5-HT only in sarpogrelate-treated rats. In sarpogrelate-treated animals, i.v. GR 127935 (310 μg/kg; 5-HT1B/1D/1F receptor antagonist) attenuated 5-CT-induced sympatho-inhibition and abolished LY344864-induced sympatho-inhibition; while GR 127935 plus SB 699551 (1 mg/kg; 5-HT5A receptor antagonist) abolished 5-CT-induced inhibition. These results confirm the cardiac sympatho-inhibitory role of 5-HT1B, 5-HT1D, and 5-HT5A receptors in both groups; nevertheless, sarpogrelate treatment specifically unmasked a cardiac sympatho-inhibition mediated by 5-HT1F receptors.

Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis

2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Enzyme Activities ◽  
Treated Group ◽  
Control Group ◽  
Puromycin Aminonucleoside ◽  
Low Level ◽  
Key Enzyme

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.

scholarly journals INSIGHTS INTO THE ROLE OF MORUS ALBA IN REVERSING OBESITY-ASSOCIATED HEPATIC STEATOSIS AND RELATED METABOLIC DISORDER IN RATS

2016 ◽  
pp. 231
Author(s):  
Hanaa H. Ahmed ◽  
Fatehya M Metwally ◽  
Hend Rashad ◽  
Asmaa M Zaazaa
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Metabolic Disorder ◽  
Ethanolic Extract ◽  
Treated Group ◽  
Morus Alba ◽  
The Other ◽  
Obese Group ◽  
Control Group

<p>ABSTRACT<br />Objective: The goal of the present study was to examine the viability of Morus alba (M. alba) ethanolic extract in repression of obesity-associated<br />hepatic steatosis and related metabolic disorder; dyslipidemia, hyperinsulinemia, and glycemic status.<br />Methods: Adult female albino rats were randomly assigned into four groups, eight rats each as follows: Group (1) control group received standard<br />rodent diet for 24 weeks. The other three groups administered high cholesterol diet for 12 weeks and served as obese group, M. alba-treated group,<br />and simvastatin-treated group.<br />Results: The current results showed an increment in thoracic circumference (TCX) and abdominal circumferences (AC) as well as body mass index<br />(BMI) in obese group. In addition, dyslipidemia, hyperinsulinemia, hyperglycemia, and insulin resistance have been elucidated in obese group.<br />Moreover, hepatic malondialdehyde (MDA), nitric oxide (NO), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin<br />values were significantly increased in obese groups versus control group. On the other hand, administration of ethanolic extract of Morus alba or<br />simvastatin could significantly lessen BMI and in addition to improve dyslipidemia in obese group. Glucose, insulin levels, and insulin resistance value<br />in serum samples demonstrated a significant reduction in obese group upon treatment with M. alba ethanolic extract or simvastatin. Furthermore,<br />noticeable depletion in hepatic MDA, NO contents, serum ALT, AST activities, and serum bilirubin level was recorded as a result of treatment with<br />either ethanolic extract of M. alba or simvastatin. Histopathological examination of liver tissue showed ballooning degeneration in the hepatocytes<br />(hepatic steatosis) associated with inflammatory cells penetration in portal zone in obese group. Meanwhile, the treatment of obese groups with<br />ethanolic extract of M. alba or simvastatin was found to restore the structural organization of the liver.<br />Conclusion: The present findings provide a novel aspect for understanding of the role of M. alba against obesity-associated liver diseases and related<br />metabolic disorder. The mechanisms underlying these effects seem to depend on the hypolipidemic potential, anti-inflammatory property, and<br />antioxidant activity of its phytochemicals.<br />Keywords: Obesity, Morus alba, Dyslipidemia, Hyperinsulinemia, Hyperglycemia, Hepatic steatosis.</p>

Protective effects of histamine on Gq-mediated relaxation in regenerated endothelium

2014 ◽  
Vol 306 (2) ◽  
pp. H286-H290 ◽  
Author(s):  
Calvin K. Chan ◽  
Song Yan Liao ◽  
Yue Lin Zhang ◽  
Aimin Xu ◽  
Hung Fat Tse ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Treated Group ◽  
Control Group ◽  
Protective Effects ◽  
Treatment Control ◽  
Porcine Coronary Artery ◽  
Endogenous Histamine ◽  
Coronary Endothelium ◽  
Treatment Control Group

In the porcine coronary artery, regenerated endothelium is dysfunctional as regards the responses to endothelium-dependent agonists. The current study aimed to determine the possible involvement of histamine in such dysfunction. Pigs were treated chronically with pyrilamine (H1 receptor inhibitor, 2 mg·kg−1·day−1) with part of their coronary endothelium and allowed to regenerate for 28 days after balloon denudation. The results showed a reduction in relaxation to bradykinin (Gq protein dependent) only in the pyrilamine-treated group (area under the curve, 269.7 ± 13.4 vs. 142.0 ± 31.0, native endothelium vs. regenerated endothelium) but not in the control group (253.0 ± 22.1 vs. 231.9 ± 29.5, native endothelium vs. regenerated endothelium). The differences in the relaxation to serotonin (Gi protein dependent) between native and regenerated endothelium were not affected by the pyrilamine treatment (control group, 106.3 ± 17.0 vs. 55.61 ± 12.7; and pyrilamine group, 106.0 ± 8.20 vs. 49.30 ± 6.31, native endothelium vs. regenerated endothelium). These findings indicate that during regeneration of the endothelium, the activation of H1 receptors by endogenous histamine may be required to maintain the endothelium-dependent Gq protein-mediated relaxation to bradykinin, suggesting a beneficial role of the monoamine in the process of endothelial regeneration.

scholarly journals Amelioration of caffeine-induced seizures by modulators of sigma, N-methyl-d-Aspartate and ryanodine receptors in mice

2017 ◽  
Vol 04 (02) ◽  
pp. 144-149
Author(s):  
Mojtaba Keshavarz ◽  
Seyyed Hoseini ◽  
Samad Akbarzadeh
Keyword(s):  
Receptor Antagonist ◽  
Synergistic Effects ◽  
Ryanodine Receptors ◽  
Treated Group ◽  
Nmda Receptor Antagonist ◽  
Clonic Seizure ◽  
Positive Control ◽  
Control Group ◽  
Gamma Aminobutyric Acid ◽  
Clonic Seizures

AbstractObjectives The aim of this study was to evaluate the antiepileptic effects of opipramol, a sigma receptor agonist, diazepam, ketamine, an N-methyl-d-Aspartate (NMDA) receptor antagonist, and dantrolene, a ryanodine receptor antagonist, against caffeine-induced seizures in mice.Methods We used caffeine (1000 mg/kg) intraperitoneally for inducing clonic and tonic-clonic seizures in male albino Swiss strain of mice. We used opipramol in three different doses (10, 20 and 50 mg/kg), ketamine (50 mg/kg), dantrolene (40 mg/kg), opipramol (20 mg/kg) plus ketamine (50 mg/kg), opipramol (20 mg/kg) plus dantrolene (40 mg/kg), diazepam (5 mg/kg as a positive control) and the vehicle 30 min before injecting caffeine. We recorded the onset of clonic, tonic-clonic seizures and the time of death of animals after using caffeine.Results Animals treated with opipramol at a dose of 50 mg/kg or diazepam had a higher onset of clonic seizure compared with the vehicle-treated group. Dantrolene alone or with opipramol (20 mg/kg) increased the latency of clonic seizure compared with the control group. Opipramol (20 and 50 mg/kg), diazepam, ketamine alone or with opipramol, and dantrolene plus opipramol increased the latency of tonic-clonic seizures in mice. All the treatments except opipramol (10 mg/kg) and dantrolene alone increased the latency of death of animals.Conclusion Opipramol attenuated seizures produced by high doses of caffeine. Moreover, the activation of sigma receptors and inhibition of ryanodine receptors may produce synergistic effects against caffeine-induced seizures. Our study may imply that different mechanisms such as inhibition of gamma-aminobutyric acid-A receptors, activation of NMDA and ryanodine receptors may contribute to the caffeine-induced seizures.

scholarly journals Protective role of ceftriaxone plus sulbactam with VRP1034 on oxidative stress, hematological and enzymatic parameters in cadmium toxicity induced rat model

2012 ◽  
Vol 5 (4) ◽  
pp. 192-200 ◽  
Author(s):  
Vivek Kumar Dwivedi ◽  
Anuj Bhatanagar ◽  
Manu Chaudhary
Keyword(s):  
Free Radical ◽  
Tissue Injury ◽  
Cadmium Toxicity ◽  
Treated Group ◽  
Protective Role ◽  
Enzymatic Activities ◽  
Exposed Group ◽  
Male Rats ◽  
Control Group

ABSTRACT We investigated the protective role of ceftriaxone plus sulbactam with VRP1034 (Elores) on hematological, lipid peroxidation, antioxidant enzymatic activities and Cd levels in the blood and tissues of cadmium exposed rats. Twenty-four male rats were divided into three groups of eight rats each. The control group received distilled water whereas group II received CdCl2 (1.5 mg/4 ml/body weight) through gastric gavage for 21 days. Group III received CdCl2 and was treated with ceftriaxone plus sulbactam with VRP1034 for 21 days. The hematological, biochemical, lipid per-oxidation levels and enzymatic parameters were measured in plasma and tissues (brain, liver and kidney) of all groups. The Cd, Zn and Fe levels were measured in blood and tissues of all groups. Our findings showed significantly decreased cadmium (p<0.001), malonaldialdehyde (p<0.001) and myloperoxidase (MPO) levels along with significantly increased hemoglobin (p<0.01), RBC (p<0.05), hematocrit (p<0.05) levels and all antioxidant enzymatic activities (SOD, CAT, GR, GPx) in plasma and tissues of ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. Delta aminolevulinate dehydratase (δ-ALAD) activity was significantly (p<0.001) increased in the blood of ceftriaxone plus sulbactam with VRP1034 treated group as compared with cadmium exposed group. The levels of hepatic and renal parameters were significantly (p<0.001) decreased in ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. These findings indicate that ceftriaxone plus sulbactam with VRP1034 acts as a potent free radical scavenger and exhibits metal chelating properties that reduce free radical mediated tissue injury and prevent dysfunction of hepatic and renal organs during metal intoxication.

268 ROLE OF ATPase MOTOR CYTOPLASMIC DYNEIN AND PRIMARY CILIA IN TESTICULAR MORPHOGENESIS

2015 ◽  
Vol 27 (1) ◽  
pp. 223
Author(s):  
C. Dores ◽  
I. Dobrinski
Keyword(s):  
Primary Cilia ◽  
Somatic Cells ◽  
Treated Group ◽  
Cytoplasmic Dynein ◽  
Control Group ◽  
Tubule Formation ◽  
Serum Free ◽  
Free Media

In vertebrates, the primary cilium is a nearly ubiquitous organelle present in somatic cells, but little is known about its function in the male gonad. We investigated the role of primary cilia in testis cells using in vitro formation of seminiferous tubules and in vitro culture of testicular somatic cells by inhibiting the primary cilium with CiliobrevinD, a cell-permeable, reversible chemical modulator that inhibits the major component of the organelle: ATPase motor cytoplasmic dynein. We analysed in vitro cultures for the presence of primary cilia and the activation of hedgehog signalling through translocation of Gli2 to the nuclei; in vitro tubule formation was evaluated by length and width of tubules formed. Methods: testicular cells were harvested from neonatal pigs by 2-step enzymatic digestion. Cells (50 × 106 mL–1) were plated on 100 mm Petri dishes in 15 mL of DMEM + 5% FBS + 50 U of penicillin and incubated at 37°C in 5% CO2 in air overnight, cells remaining in suspension and those slightly attached were removed and the somatic cells attached were trypsinized to obtain a single cell suspension, and then submitted to two different protocols: in vitro culture (A) or in vitro tubule formation (B), n = 5 replicates each. For A, somatic cells were replated on coverslips in 24-well plates and cultured in serum free media for 48 h, then for the treated group, 10 mM of CiliobrevinD was added for 24 h, attached cells from control and treated groups were fixed in 4% PFA and characterised by immunocytochemistry for ARL13B, Vimentin, and Gli2. For B: 1 × 106 cells were added to 24-well plates coated with 1 : 1 diluted Matrigel, the control group was kept in serum free media and to the treated group was added 20 mM CiliobrevinD at Day 0. Results: A) primary cilia were present in 89.3 ± 2.3% of cells cultured in serum-free media for the control group and Gli2 was located in the nuclei of 90.2 ± 1.2% of cells; in the CiliobrevinD-treated group the percentage of primary cilia decreased (P < 0.05) to 3.1 ± 2.5% and nuclear Gli2 to 3.9 ± 0.7; B) tubules formed in the control group were significantly longer and wider than the ones formed when CiliobrevinD was added (9.91 ± 0.35 v. 5.540 ± 1.08 mm and 339.8 ± 55.78 v. 127.2 ± 11.9 µm, respectively, P < 0.05 by Student's t-test). In conclusion, the inhibition of ATPase motor cytoplasmic dynein perturbs formation of primary cilia in testicular somatic cells, blocks Hedgehog signalling, and impairs in vitro tubule formation. Therefore, primary cilia on testicular somatic cells appear to be essential for testicular morphogenesis.Research was supported by 5 R01 OD016575-13.

Short term chronic toxicity of tributyltin on the testes of adult albino rats and the possible protective role of omega-3

2020 ◽  
pp. 096032712094745
Author(s):  
Marwa G Ahmed ◽  
Mona El-Demerdash Ibrahim ◽  
Hoda R El Sayed ◽  
Samah M Ahmed
Keyword(s):  
Treated Group ◽  
Toxic Effects ◽  
Cellular Damage ◽  
Antioxidant Defenses ◽  
Control Group ◽  
Albino Rats ◽  
Omega 3 ◽  
Group I

The declining rate of male fertility is a growing concern. Tributyltin (TBT) is a well-known endocrine disruptor (ED), that induces imposex in female gastropods and is widely used in various industrial applications. The aim of this study was to evaluate the toxic effects of TBT on the testes of adult albino rats and the possible role of omega-3. Forty two adult male albino rats were divided into five groups; control group (Group I) and four experimental groups: omega-3 treated group, TBT treated group, TBT & omega-3 treated group and follow up group. At the end of the study, the rats were subjected to biochemical, histological, immunohistochemical staining for Ki-67 and seminal examinations. Our results clarfied that TBT induced a significant decrease in testosterone, FSH, LH and serum glutathione peroxidase levels and a significant increase in the serum Malondialdehyde as compared to the control group. Tributyltin induced disorganization and shrinkage of seminiferous tubules, apoptosis, cellular damage and marked reduction in the germinal epithelium. A significant decrease in the cell proliferation and arrested spermatogenesis were also detected. Seminal analysis of TBT group showed a significant affection of all parameters as compared to other groups. Omega-3 ameliorated all of these hazardous effects. Follow up group still showed toxic effects. In conclusion, TBT has a toxic effect on the testis. Increased testicular oxidative stress, cellular damage and arrest of spermatogenesis with attenuation in antioxidant defenses are all contributing factors. Omega-3 can protect against TBT induced reproductive toxicity.

scholarly journals Staphylococcus aureus Infection Induced Oxidative Imbalance in Neutrophils: Possible Protective Role of Nanoconjugated Vancomycin

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Subhankari Prasad Chakraborty ◽  
Panchanan Pramanik ◽  
Somenath Roy
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Cell Damage ◽  
Treated Group ◽  
Protective Role ◽  
Control Group ◽  
Similar Dose ◽  
Cellular Components

Staphylococcus aureus infection causes oxidative stress in neutrophils. The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was aimed to test the protective role of nanoconjugated vancomycin against vancomycin-sensitive Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infection induced oxidative stress in neutrophils. VSSA- and VRSA-infection were developed in Swiss mice by intraperitoneal injection of 5×106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was treated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was treated to VSSA and VRSA infected mice at similar dose, respectively, for 10 days. The result reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, and nitrite generation and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group; which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These finding suggests the potential use and beneficial protective role of nanoconjugated vancomycin against VSSA and VRSA infection induced oxidative imbalance in neutrophils.

Studies on salt tolerance of sheep. V. The tolerance of sheep for mixtures of sodium chloride, sodium carbonate, and sodium bicarbonate in the drinking water

1963 ◽  
Vol 14 (6) ◽  
pp. 815 ◽  
Author(s):  
AW Peirce
Keyword(s):  
Carbon Dioxide ◽  
Drinking Water ◽  
Sodium Chloride ◽  
Rain Water ◽  
Control Group ◽  
Health Food ◽  
Water Control ◽  
Entire Experiment ◽  
Daily Intakes ◽  
Saline Solutions

Six groups, each of six sheep, were fed in pens for 15 months on a ration of chaffed lucerne and wheaten hays. One group was offered rain-water to drink, another group was offered 1.30% sodium chloride, whereas the others were offered one of the following mixtures of sodium chloride, carbonate, and bicarbonate: 1.26 + 0.015 + 0.025, 1.21 + 0.04 + 0.06, 1.12 + 0.08 + 0.13, and 0.95 + 0.161+ 0.25%. The intake of all saline solutions was higher than that of rain-water, ranging from 150% above for 1.30% sodium chloride to 60% above for the highest level of carbonates; the mean daily intakes for the entire experiment by the six groups were 2.6, 6.6, 4.8, 5.7, 5.8, and 4.2 l. respectively. The intake also increased in all groups with temperature, being 40–70% higher in the hottest months than in the coldest months.Weight increase was less from 6 months onward in the group receiving 1.30% sodium chloride, and was less at certain times only in the experiment in the groups receiving 0.04 or 0.10% carbonates, than in that receiving rain-water (control group). There were no differences in weight increase between the control group and the groups receiving the highest concentrations (0.21 and 0.41%) of carbonates The saline drinking waters had no effect on the concentrations of sodium, potassium, calcium, magnesium, or chloride in the blood plasma. The concentration of carbon dioxide was higher, for the last year of the experiment, in the blood of the control group, and, for approximately one-third of the experiment, in that of the group receiving the highest level of carbonates in its drinking water, than in that of any of the groups receiving lower levels of carbonates. There were differences in blood carbon dioxide on one occasion only between the control group and that receiving the highest level of carbonates. None of the solutions used in the experiment had any adverse effect on the general health, food consumption or wool production of the sheep.

scholarly journals Toxicology of Lapachol in rats: embryolethality

2001 ◽  
Vol 61 (1) ◽  
pp. 171-174 ◽  
Author(s):  
M. de O. GUERRA ◽  
A. S. B. MAZONI ◽  
M. A. F. BRANDÃO ◽  
V. M. PETERS
Keyword(s):  
Therapeutic Potential ◽  
Treated Group ◽  
Vehicle Group ◽  
Control Group ◽  
Corpora Lutea ◽  
Water Control ◽  
Chi Square ◽  
Significance Level ◽  
Chi Square Test ◽  
Teratogenic Potential

Lapachol is a naphtoquinone with therapeutic potential against enterovirus, Chagas disease and is also used as an antimalarial and antiinflamatory agent. In order to study teratogenic potential of Lapachol, pregnant Wistar rats were treated with 0.5 ml of distilled water (control group); 0.5 ml of hydroalcoholic solution (vehicle group) and 10 mg of Lapachol in 0.5 ml of hydroalcoholic solution (treated group) by oral gavage from the 8th to the 12th day of pregnancy. The following variables were observed: maternal body weight on days 1, 6, l5 and 21 and food intake on days 2, 6, 15 and 21 of pregnancy. The number of live and dead fetuses and the sites of resorptions were counted. The ovaries were weighed and the corpora lutea were counted. Data were analyzed by ANOVA-one way, Dunnett test and the chi square test. Significance level test alpha = 0.05. Results have shown that mothers were unaffected but there were a 99.2% of fetus mortality, indicative of a strong abortifacient effect of Lapachol in rats.

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