Dronedarone: the effect of diet-induced obesity on its metabolism and experimental hyperlipidemia on its metabolism and tissue distribution in the rat

2020 ◽  
Vol 98 (3) ◽  
pp. 177-181
Author(s):  
Yousef A. Bin Jardan ◽  
Ali Abdussalam ◽  
Ayman O.S. El-Kadi ◽  
Dion R. Brocks
Keyword(s):  
Substrate Inhibition ◽  
Poloxamer 407 ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Experimental Hyperlipidemia ◽  
Intestinal Microsomes ◽  
And Control ◽  
High Calorie

Dronedarone biodistribution in hyperlipidemia and dronedarone metabolism in hyperlipidemia or obesity were assessed. Male Sprague–Dawley rats were given either normal standard chow with water or various high-fat or high-carbohydrate diets for 14 weeks. There was also a nonobese hyperlipidemic group given poloxamer 407 intraperitoneally. Liver and intestinal microsomes were prepared and the metabolic conversion of dronedarone to desbutyldronedarone was followed. A biodistribution study of dronedarone given orally was conducted in hyperlipidemic and control normolipidemic rats. The metabolism of dronedarone to desbutyldronedarone in control rats was consistent with substrate inhibition. However in the treatment groups, the formation of desbutyldronedarone did not follow substrate inhibition; hyperlipidemia and high-calorie diets created remarkable changes in dronedarone metabolic profiles and reduction in formation velocities. Tissue concentrations of dronedarone were much higher than in plasma. Furthermore, in hyperlipidemia, plasma and lung dronedarone concentrations were significantly higher compared to normolipidemia.

Relationship between sympathetic activity and diet-induced obesity in two rat strains

1983 ◽  
Vol 245 (3) ◽  
pp. R364-R371 ◽  
Author(s):  
B. E. Levin ◽  
J. Triscari ◽  
A. C. Sullivan
Keyword(s):  
Sympathetic Activity ◽  
Caloric Intake ◽  
Sprague Dawley ◽  
Rat Strains ◽  
Sympathetic Function ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Calorie Diet ◽  
High Calorie Diet ◽  
High Calorie

Chronic diet-induced obesity developed in 50-60% of male Sprague-Dawley rats fed a relatively high-calorie diet for 90 days. The remaining rats decreased their caloric intake and resisted the development of obesity. All male Fischer F-344 rats fed this diet for 85 days became obese but to only half the degree of the obese Sprague-Dawley rats. The development of chronic obesity in both rat strains was associated with decreased norepinephrine (NE) levels in hearts and aortas and decreased NE turnover in aortas compared with chow-fed controls. However, 40-50% of the Sprague-Dawley rats did not become obese on this diet, yet showed similar findings suggesting an effect of dietary composition on sympathetic function. The more profoundly obese Sprague-Dawley rats additionally showed decreased or absent NE turnover in their hearts and pancreases. Since sympathetic function in both strains of rats with diet-induced obesity was either depressed or normal, it appears unlikely that the initial enhancement of sympathetic activity seen during short-term overfeeding plays an important continuing role in combating more chronic states of obesity in the rat.

Glucose-induced norepinephrine levels and obesity resistance

1987 ◽  
Vol 253 (3) ◽  
pp. R475-R481 ◽  
Author(s):  
B. E. Levin ◽  
A. C. Sullivan
Keyword(s):  
Weight Gain ◽  
Caloric Intake ◽  
Sympathetic Activation ◽  
Glucose Load ◽  
Sprague Dawley ◽  
Intravenous Glucose ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Calorie Diet ◽  
High Calorie

The value of glucose-stimulated sympathetic activation in differentiating rats that would subsequently resist or develop diet-induced obesity (DIO) when chronically fed a high-calorie diet (CM) enriched in fat and sucrose was tested in 3-mo-old male Sprague-Dawley rats. While the rats were on chow the areas under the curve for plasma glucose, insulin, and norepinephrine (NE) levels were measured for 60 min after an intravenous glucose load (1 g/kg). Half of the rats then switched to the CM diet for 14 wk developed DIO with 54% more weight gain and 205% heavier retroperitoneal fat pads; half [diet resistant (DR)] had weight gain and pad weights comparable to chow-fed controls. Caloric intake was comparable in all animals. NE areas after intravenous glucose loads were 54% lower in DR than DIO rats, and there was a positive correlation (r = 0.63) between these NE areas and subsequent weight gain on the CM diet. Areas under the insulin curve correlated with subsequent weight gain on chow (r = 0.71) but not the CM diet. These results suggest that rats predisposed to become DR on the CM diet have dampened sympathetic activation after a glucose load, possibly because of heightened end-organ responsiveness to NE.

EFFECT OF EXPERIMENTALLY INDUCED THYROIDITIS ON BIOSYNTHESIS OF THYROXINE IN RATS

1969 ◽  
Vol 62 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Colum A. Gorman ◽  
James W. Anderson ◽  
Eunice V. Flock ◽  
Charles A. Owen ◽  
Khalil G. Wakim
Keyword(s):  
Intravenous Administration ◽  
Hashimoto's Thyroiditis ◽  
Sprague Dawley ◽  
Thyroid Extract ◽  
Histologic Appearance ◽  
Gland Weight ◽  
Sprague Dawley Rats ◽  
Thyroid Glands ◽  
And Control ◽  
Experimentally Induced

ABSTRACT Thyroiditis was induced in Sprague-Dawley rats by repeated immunization with thyroid extract and Freund's adjuvant. Immunized and control animals were killed at intervals up to 6 hours after intravenous administration of 131I as iodide at 5, 8 and 10 weeks after the first injection. Radioiodinated compounds in the thyroid glands were identified chromatographically. Evidence of moderate thyroiditis was present (histologic appearance, gland weight, and protein-bound iodine-butanol-extractable iodine difference) but the rate of incorporation of radioiodide into thyroxine, the percentage of radioactivity in the gland as iodide, and the MIT/DIT ratio were not significantly different in immunized and control animals. The MIT/DIT ratio was found to vary with time after 131I administration in both immunized and control animals. These studies did not uncover a defect in organification of iodide in experimental thyroiditis similar to that described by others in humans with Hashimoto's thyroiditis.

Defense of differfing body weight set points in diet-induced obese and resistant rats

1998 ◽  
Vol 274 (2) ◽  
pp. R412-R419 ◽  
Author(s):  
Barry E. Levin ◽  
Richard E. Keesey
Keyword(s):  
Body Weight ◽  
Diet Composition ◽  
Energy Homeostasis ◽  
Energy Content ◽  
Sprague Dawley ◽  
Fat Pad ◽  
Insulin Levels ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Plasma Leptin

Among outbred Sprague-Dawley rats, approximately one-half develop diet-induced obesity (DIO) and one-half are diet resistant (DR) on a diet relatively high in fat and energy content (HE diet). Here we examined the defense of body weight in these two phenotypes. After HE diet for 13 wk, followed by chow for 6 wk, DR rats gained weight comparably but their plasma leptin levels fell to 54% of chow-fed controls. When a palatable liquid diet (Ensure) was added for 13 wk, other DR rats became obese. But when switched to chow, their intakes fell by 60%, and body and retroperitoneal (RP) fat pad weights and plasma leptin and insulin levels all declined for 2 wk and then stabilized at control levels after 6 wk. In contrast, comparably obese DIO rats decreased their intake by only 20%, and their weights plateaued when they were switched to chow after 13 wk on HE diet. When a subgroup of these DIO rats was restricted to 60% of prior intake, their weights fell to chow-fed control levels over 2 wk. But their leptin and insulin levels both fell disproportionately to 30% of controls. When no longer restricted, their intake and feed efficiency rose immediately, and their body and RP pad weights and leptin and insulin levels rose to those of unrestricted DIO rats within 2 wk. Thus diet and genetic background interact to establish high (DIO) or low (DR) body weight set points, which are then defended against subsequent changes in diet composition and/or energy availability. If leptin affects energy homeostasis, it does so differentially in DIO vs. DR rats since comparably low and high levels were associated with differing patterns of weight change between the two phenotypes.

scholarly journals Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

2014 ◽  
Vol 40 (4) ◽  
pp. 421-424 ◽  
Author(s):  
Igor Bastos Polonio ◽  
Milena Marques Pagliareli Acencio ◽  
Rogério Pazetti ◽  
Francine Maria de Almeida ◽  
Bárbara Soares da Silva ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Experimental Model ◽  
Ventricular Hypertrophy ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Sprague Dawley ◽  
Control Groups ◽  
Right Heart ◽  
Sprague Dawley Rats ◽  
And Control

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

scholarly journals Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation

2012 ◽  
Vol 27 (5) ◽  
pp. 301-305 ◽  
Author(s):  
Baohua Zhu ◽  
Chuanming Tong ◽  
Weitao Guo ◽  
Rong Pu ◽  
Guoping Zhang ◽  
...  
Keyword(s):  
Survival Time ◽  
Hyperacute Rejection ◽  
Cobra Venom ◽  
Control Group ◽  
Sprague Dawley ◽  
Donor Liver ◽  
Cobra Venom Factor ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
And Control

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.

scholarly journals Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Na Cui ◽  
Hao Wang ◽  
Yun Long ◽  
Longxiang Su ◽  
Dawei Liu
Keyword(s):  
Escherichia Coli ◽  
Vascular Endothelium ◽  
Free Water ◽  
Endothelial Glycocalyx ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Protein Levels ◽  
Sprague Dawley Rats ◽  
The Matrix ◽  
Rat Thoracic Aorta

The aim of this study is to determine the mechanism of sepsis-induced vascular hyperpermeability and the beneficial effect of glucocorticoid in protecting vascular endothelium. Male Sprague-Dawley rats were given either a bolus intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli055:B5, 10 mg/kg, Sigma) or vehicle (pyrogen-free water). Animals of treatment groups were also given either dexamethasone (4 mg/kg, 30 min prior to LPS injection) or the matrix metalloproteinases (MMPs) inhibitor doxycycline (4 mg/kg, 30 min after LPS injection). Both activities and protein levels of MMP-2p<0.001and MMP-9p<0.001were significantly upregulated in aortic homogenates from LPS-treated rats, associated with decreased ZO-1p<0.001and syndecan-1p=0.011protein contents. Both dexamethasone and doxycycline could significantly inhibit MMPs activity and reserve the expressions of ZO-1 and syndecan-1. The inhibition of MMPs by dexamethasone was significantly lower than that by doxycycline, while the rescue of syndecan-1 expression from LPS-induced endotoxemic rat thoracic aorta was significantly higher in the dexamethasone-treated compared to the doxycycline-treatedp=0.03. In conclusion, activation of MMPs plays important role in regulating ZO-1 and syndecan-1 protein levels in LPS mediated endothelial perturbation. Both dexamethasone and doxycycline inhibit activation of MMPs that may contribute to the rescue of ZO-1 and syndecan-1 expression.

Changes in total body calcium balance with exercise in the rat

1983 ◽  
Vol 55 (1) ◽  
pp. 201-204 ◽  
Author(s):  
A. D. LeBlanc ◽  
H. J. Evans ◽  
P. C. Johnson ◽  
S. Jhingran
Keyword(s):  
Least Squares ◽  
Voluntary Exercise ◽  
Calcium Balance ◽  
Sprague Dawley ◽  
Total Body Calcium ◽  
Sprague Dawley Rats ◽  
Least Squares Fit ◽  
Significant Change ◽  
Total Body ◽  
And Control

The purpose of this study was to evaluate the effect of deconditioning on the total body calcium in rats. Two separate experiments were performed using female Sprague-Dawley rats, 187-266 days of age. Total body calcium was measured in experimental and control rats during and following several weeks of voluntary exercise. The slope from the least-squares fit of total body calcium with time was used to obtain an average calcium balance for each animal during each study period. In both groups the exercised rats had a significantly decreased calcium balance after cessation of exercise, whereas no significant change was seen in nonexercised controls. In both groups, the exercised animals gained calcium at a significantly greater rate than controls. Our findings indicate that while exercised rats may gain calcium at a faster rate compared with nonexercising controls, the rate of gain following cessation of exercise is less than the controls.

scholarly journals TRANSFERSOME GEL FORMULATION OF AN ETHANOL EXTRACT OF APPLES (MALUS DOMESTICA MILL) CONTAINING ANTIOXIDANTS AND IN VITRO PENETRATION TESTING USING FRANZ DIFFUSION CELLS

2017 ◽  
Vol 9 ◽  
pp. 32 ◽  
Author(s):  
Nurarita Fadila Zesiorani ◽  
Effionora Anwar
Keyword(s):  
Ethanol Extract ◽  
Sprague Dawley ◽  
Diffusion Cells ◽  
Sprague Dawley Rats ◽  
Apple Peel ◽  
Franz Diffusion Cells ◽  
Drug Efficiency ◽  
And Control ◽  
Peel Extract

Objective: This study aims to formulate and characterize a transfersome apple peel extract, formulate it into a gel, and compare it with a control gelmade without transfersome.Methods: Both gels were evaluated, stability tested, and penetration tested using Franz diffusion cells on the skin of female Sprague-Dawley rats. Thetransfersome preparations were formulated with different concentrations of the active substance, quercetin: 0.5% (F1); 0.7% (F2), and 1.0% (F3).Results: Based on the characterization results, F1 was selected as the optimum gel formulation because it had spherical morphology, a Dmean volume of106.44±2.70 nm, a polydispersity index of 0.078±0.01, a zeta potential of −49.96±2.05 mV, and a drug efficiency entrapment percentage of 78.78±0.46%.The cumulative amount of quercetin that was penetrated with the transfersome gel was 1514.41±26.31 μg/cm2, whereas the penetration with thecontrol gel extract was 1133.62±18.96 μg/cm2. The cumulative percentages of the penetrated gel transfersome and gel extract were 78.40±1.89%and 49.89±0.88%, respectively. The fluxes of transfersome gel and control gel extract were 52.33±0.11 μg/cm²/hrs and 40.89±0.68 μg/cm²/hrs,respectively.Conclusions: Based on these results, it can be concluded that the gel with transfersome exhibited better penetration than the gel extract alone.

scholarly journals Effects of Aqueous Quassia amara L. (Korales) Leaf Extract on the Cardiovascular and Respiratory Functions of Male Sprague-Dawley Rats

2018 ◽  
Vol 52 (6) ◽  
Author(s):  
Maria Concepcion C. Sison ◽  
Lynn Crisanta R. Panganiban ◽  
Daisy Mae A. Bagaoisan ◽  
Nelia P. Cortes-Maramba
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Leaf Extract ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Respiratory Flow ◽  
Sprague Dawley Rats ◽  
Parallel Group ◽  
Aqueous Leaf Extract ◽  
Quassia Amara

Objective. To To evaluate potential effects of the aqueous extract of Quassia amara L. leaves on the cardiovascular and respiratory systems of adult male Sprague- Dawley rats. Methods. The cardiovascular and respiratory effects of the Quassia amara L. leaf extract on adult male SpragueDawley rats were assessed using non-invasive blood pressure (NIBP) determination and head-out plethysmography, respectively, in a randomized, parallel group study. Mean observations of blood pressure and heart rate were recorded at different time periods after dosing. Respiratory flow and irritation effects were evaluated using mean observations of respiratory rate (RR), tidal volume (TV), mid-expiratory flow rate (EF50), time of inspiration (TI) and expiration (TE), and time of break (TB) and pause (TP). Results. There were no significant differences among the control and the treatment groups in SBP, DBP and HR parameters. The extract showed statistically significant effect on mean RR by time period (F=2.45, p=0.0234), trends over time of TV among the dose groups (F=2.00, p=0.0202), and EF50 among dose groups ((F=3.11, p=0.0422). However, these did not correlate with the changes in the time of break (TB) and time of pause (TP) which are more sensitive and specific tests for respiratory irritation. Conclusion. Aqueous leaf extract of Quassia appeared to have no significant effects on SBP, DPB, Pulse pressure, and HR. There are no conclusive dose-related respiratory flow or pulmonary irritation effects.

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