scholarly journals Simultaneous Evaluation of the Influence of Panax ginseng on the Pharmacokinetics of Three Diester Alkaloids after Oral Administration of Aconiti Lateralis Radix in Rats Using UHPLC/QQQ-MS/MS

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Liang Yang ◽  
Yuguang Wang ◽  
Guangyao Huang ◽  
Jian Li ◽  
Zhaoyan Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Panax Ginseng ◽  
Day Treatment ◽  
Control Group ◽  
Plasma Samples ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Simultaneous Evaluation ◽  
Reproducible Method

Objectives. To investigate whether Panax ginseng (P. ginseng) could affect the metabolism of Diester Alkaloids (DAs) derived from Aconiti Lateralis Radix in vivo. Methods and Results. 24 male Sprague-Dawley rats were randomized for 7-day treatment with P. ginseng (low, middle, and high), or vehicle. Aconiti Lateralis Radix was administered orally to each group on the 8th day. Plasma samples were collected, and Xevo TQ-S was used to detect the concentration of aconitine, mesaconitine, and hypaconitine in plasma. We describe a fast and reproducible method to detect the concentration of aconitine, mesaconitine, and hypaconitine in plasma. Compared to the control group, the AUC(0-t) of three DAs increased in both the middle and high dosing groups. The Vz/F of three DAs in these groups as well as the CLz/F of aconitine in all P. ginseng groups and the CLz/F of mesaconitine and hypaconitine in P. ginseng middle and high groups were decreased compared to the control group. Conclusion. Orally administrated P. ginseng potentially inhibits the metabolism of DAs from Aconiti Lateralis Radix in rats.

scholarly journals Acute and Subchronic Toxicity Study ofEuphorbia hirtaL. Methanol Extract in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kwan Yuet Ping ◽  
Ibrahim Darah ◽  
Yeng Chen ◽  
Subramaniam Sreeramanan ◽  
Sreenivasan Sasidharan
Keyword(s):  
Body Weight ◽  
Toxicity Study ◽  
Morphological Alteration ◽  
Control Group ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Methanolic Extracts ◽  
Sprague Dawley Rats ◽  
Significant Difference

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.

Tissue Deposition of the Insect Repellent DEET and the Sunscreen Oxybenzone From Repeated Topical Skin Applications in Rats

2010 ◽  
Vol 29 (6) ◽  
pp. 594-603 ◽  
Author(s):  
Daryl J. Fediuk ◽  
Tao Wang ◽  
Joshua E. Raizman ◽  
Fiona E. Parkinson ◽  
Xiaochen Gu
Keyword(s):  
Day Treatment ◽  
Skin Permeation ◽  
Application Site ◽  
Insect Repellent ◽  
Sprague Dawley ◽  
Combined Application ◽  
Sprague Dawley Rats ◽  
Rat Astrocytes ◽  
Topical Applications

Insect repellent N,N-diethyl- m-toluamide (DEET) and sunscreen oxybenzone are capable of enhancing skin permeation of each other when applied simultaneously. We carried out a cellular study in rat astrocytes and neurons to assess cell toxicity of DEET and oxybenzone and a 30-day study in Sprague-Dawley rats to characterize skin permeation and tissue disposition of the compounds. Cellular toxicity occurred at 1 µg/mL for neurons and 7-day treatment for astrocytes and neurons. DEET and oxybenzone permeated across the skin to accumulate in blood, liver, and brain after repeated topical applications. DEET disappeared from the application site faster than oxybenzone. Combined application enhanced the disposition of DEET in liver. No overt sign of behavioral toxicity was observed from several behavioral testing protocols. It was concluded that despite measurable disposition of the study compounds in vivo, there was no evidence of neurotoxicological deficits from repeated topical applications of DEET, oxybenzone, or both.

scholarly journals A Novel Strategy to Enhance Microfracture Treatment With Stromal Cell-Derived Factor-1 in a Rat Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Taylor Mustapich ◽  
John Schwartz ◽  
Pablo Palacios ◽  
Haixiang Liang ◽  
Nicholas Sgaglione ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cartilage Repair ◽  
Osteochondral Defect ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stromal Cell Derived Factor ◽  
Empty Control

BackgroundMicrofracture is one of the most widely used techniques for the repair of articular cartilage. However, microfracture often results in filling of the chondral defect with fibrocartilage, which exhibits poor durability and sub-optimal mechanical properties. Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for mesenchymal stem cells (MSCs) and is expressed at high levels in bone marrow adjacent to developing cartilage during endochondral bone formation. Integrating SDF-1 into an implantable collagen scaffold may provide a chondro-conductive and chondro-inductive milieu via chemotaxis of MSCs and promotion of chondrogenic differentiation, facilitating more robust hyaline cartilage formation following microfracture.ObjectiveThis work aimed to confirm the chemoattractive properties of SDF-1 in vitro and develop a one-step method for incorporating SDF-1 in vivo to enhance cartilage repair using a rat osteochondral defect model.MethodsBone marrow-derived MSCs (BMSCs) were harvested from the femurs of Sprague–Dawley rats and cultured in low-glucose Dulbecco’s modified Eagle’s medium containing 10% fetal bovine serum, with the medium changed every 3 days. Passage 1 MSCs were analyzed by flow cytometry with an S3 Cell Sorter (Bio-Rad). In vitro cell migration assays were performed on MSCs by labeling cells with carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE; Bio-Rad). For the microfracture model, a 1.6-mm-diameter osteochondral defect was created in the femoral trochleae of 20 Sprague–Dawley rats bilaterally until bone marrow spillage was seen under saline irrigation. One knee was chosen at random to receive implantation of the scaffold, and the contralateral knee was left unfilled as an empty control. Type I collagen scaffolds (Kensey Nash) were coated with either gelatin only or gelatin and SDF-1 using a dip coating process. The rats received implantation of either a gelatin-only scaffold (N = 10) or gelatin-and-SDF-1 scaffold (N = 10) at the site of the microfracture. Femurs were collected for histological analyses at 4- and 8-week time points post-operatively, and sections were stained with Safranin O/Fast Green. The samples were graded blindly by two observers using the Modified O’Driscoll score, a validated scoring system for chondral repair. A minimum of 10 separate grading scores were made per sample and averaged. Quantitative comparisons of cell migration in vitro were performed with one-way ANOVA. Cartilage repair in vivo was also compared among groups with one-way ANOVA, and the results were presented as mean ± standard deviation, with P-values < 0.05 considered as statistically significant.ResultsMSC migration showed a dose–response relationship with SDF-1, with an optimal dosage for chemotaxis between 10 and 100 ng/ml. After scaffold implantation, the SDF-1-treated group demonstrated complete filling of the cartilage defect with mature cartilage tissue, exhibiting strong proteoglycan content, smooth borders, and good incorporation into marginal cartilage. Modified O’Driscoll scores after 8 weeks showed a significant improvement of cartilage repair in the SDF-1 group relative to the empty control group (P < 0.01), with a trend toward improvement when compared with the gelatin-only-scaffold group (P < 0.1). No significant differences in scores were found between the empty defect group and gelatin-only group.ConclusionIn this study, we demonstrated a simple method for improving the quality of cartilage defect repair in a rat model of microfracture. We confirmed the chemotactic properties of SDF-1 on rat MSCs and found an optimized dosage range for chemotaxis between 10 and 100 ng/ml. Furthermore, we demonstrated a strategy to incorporate SDF-1 into gelatin–collagen I scaffolds in vivo at the site of an osteochondral defect. SDF-1-treated defects displayed robust hyaline cartilage resurfacing of the defect with minimal fibrous tissue, in contrast to the empty control group. The results of the in vitro and in vivo studies together suggest that SDF-1-mediated signaling may significantly improve the quality of cartilage regeneration in an osteochondral defect.

Effect of chronic endothelin blockade in hyperinsulinemic hypertensive rats

1995 ◽  
Vol 269 (6) ◽  
pp. H2017-H2021 ◽  
Author(s):  
S. Verma ◽  
S. Bhanot ◽  
J. H. McNeill
Keyword(s):  
Blood Vessel ◽  
Plasma Insulin ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Normal Rat ◽  
Plasma Insulin Levels ◽  
Old Rats ◽  
Normotensive Control

Evidence suggests that hyperinsulinemia may be causally related to the development of high blood pressure (BP) in fructose-hypertensive (FH) rats. Because plasma insulin has been shown to modulate endothelin (ET) release in vivo, we hypothesized that hyperinsulinemia may provide a continual stimulus for ET release, which could increase BP by altering plasma or blood vessel ET levels. To test this hypothesis, we studied the effect of chronic ET-receptor blockade (by using bosentan, a noncompetitive ET antagonist) on plasma insulin levels, plasma ET levels, blood vessel ET content, and BP in FH rats. Chronic oral bosentan treatment (100 mg.kg-1.day-1) was initiated in 6-wk-old Sprague-Dawley rats. One week after bosentan treatment was started, rats were fed either normal rat chow or a fructose-enriched diet. Plasma insulin, plasma glucose, and systolic BP were measured weekly. At termination (in 15-wk-old rats), plasma ET levels and total mesenteric ET content were determined. Bosentan treatment caused a sustained decrease in BP in the FH rats (treated 130 +/- 4 vs. untreated 149 +/- 2 mmHg, P < 0.001) but had no effect in the normotensive control group. FH rats had a higher total mesenteric ET content compared with the control group (21.5 +/- 3.2 vs. 14.1 +/- 2.1 fmol, P < 0.05). Bosentan treatment did not alter total mesenteric ET content (treated 18.8 +/- 5 fmol, P > 0.05 vs. untreated) nor did it affect plasma insulin or ET levels in any group. These data suggest that ET may be involved in the development of high BP in FH rats. Whether ET represents an intermediate, linking hyperinsulinemia to hypertension in rats, or is an independent hypertensinogenic mechanism remains to be determined.

scholarly journals Effect of Chronic Exposure to Dexamethasone on Rocuronium-induced Neuromuscular Blockade and Sugammadex Reversal: an in Vivo Study on Rats

2021 ◽  
Author(s):  
Ha Yeon Park ◽  
Heyran Choi ◽  
Yong Beom Kim ◽  
Seok Kyeong Oh ◽  
Taehoon Kim ◽  
...  
Keyword(s):  
Neuromuscular Blockade ◽  
Chronic Exposure ◽  
Recovery Time ◽  
Medical Center ◽  
Control Group ◽  
Sprague Dawley ◽  
Dexamethasone Group ◽  
Sprague Dawley Rats ◽  
Train Of Four

Abstract Background: Chronic exposure to glucocorticoids is associated with resistance to nondepolarising neuromuscular blocking agents. Therefore, we hypothesised that sugammadex-induced recovery in subjects with chronic exposure to dexamethasone was faster than that in subjects without dexamethasone exposure. Objective: To evaluate the recovery profile of rocuronium-induced neuromuscular blockade after sugammadex administration in rats. Design: An in vivo study on rats.Setting: Asan Institute for Life Sciences, Asan Medical Center, Korea, from April 2017 to October 2017.Animals: Thirty-six male Sprague-Dawley rats.Intervention: Sprague–Dawley rats were allocated to three groups (dexamethasone group, control group, and pair-fed group) for the in vivo study. Dexamethasone group received daily intraperitoneal injections of dexamethasone 500 μg kg-1 or 0.9% saline for 15 days. On the sixteenth day, 3.5 mg kg-1 of rocuronium was administered to achieve complete neuromuscular blockade. Main outcome measures: The recovery time to a train-of-four ratio Results: There were no significant differences in the recovery time to train-of-four ratio to 0.9 among the groups (P = 0.531). The time to second twitch of train-of-four recovery that indicated the duration of rocuronium-induced neuromuscular blockade was significantly shorter in Group D than in Groups C and P (P = 0.001). Conclusion: As previously reported, resistance to rocuronium was observed in rats with chronic exposure to dexamethasone. However, the neuromuscular recovery time after sugammadex administration was not significantly different between groups.

Pharmacokinetics of bio-shell-silver-core nanoparticles (AgNP) in Sprague-Dawley Rats – In vivo study

2021 ◽  
Vol 09 ◽  
Author(s):  
Asra Parveen ◽  
Vijay kumar B. Malashetty ◽  
Sushruta Marla ◽  
Shanth Reddy ◽  
Sidramappa Sirsand ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Body Weight ◽  
Biomedical Applications ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Potential Toxicity ◽  
Target Organs ◽  
Sprague Dawley Rats

Background: Silver nanoparticles have been widely used in the field of nanomedicine. A comprehensive understanding of their pharmacokinetics is crucial for proper risk assessment and safe biomedical applications. Objectives: The purpose of this study was to investigate the safety of silver nanoparticles by determining its potential toxicity following 28 days administration in Sprague Dawley rats. Method: The silver nanoparticles were administered by intravenous injection at the doses of 100, 200 and 500 µg/kg body weight for 28 consecutive days. Animals in the control group were received sterile water for injection. Each group consists of 10 male and 10 female rats. Results: No treatment related effects were seen in any of the parameters monitored in rats given 100, 200 and 500 µg/kg body weight/day of silver nanoparticles. Conclusion: The study proved that the use of up to 500 µg/kg body weight biosynthesized silver nanoparticles have no toxic effect in the target organs and found safe. However, the safety of the nanoparticles might be attributed to the covering of biological moieties on nanoparticles. Hence, the biofunctionalized nanoparticles can be safely used by selecting the required size and dose in medicines and drug delivery systems.

Selective A1 adenosine receptor antagonism augments beta-adrenergic-induced renin release in vivo

1995 ◽  
Vol 269 (4) ◽  
pp. F469-F479 ◽  
Author(s):  
C. A. Pfeifer ◽  
F. Suzuki ◽  
E. K. Jackson
Keyword(s):  
Plasma Renin ◽  
Renin Release ◽  
Control Group ◽  
Sprague Dawley ◽  
Endogenous Adenosine ◽  
Adenosine A2 Receptor ◽  
Sprague Dawley Rats ◽  
Receptor Interactions ◽  
A1 Receptor

This study determines, in vivo, whether endogenous adenosine/A1 receptor interactions at juxtaglomerular cells restrain the release of renin induced by receptor-mediated activation of the adenosine 3',5'–cyclic monophosphate pathway and whether endogenous adenosine/A2 receptor interactions diminish this restraining response. The following four pharmacological probes were employed: 1) 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and 2) FK-453, both selective A1 receptor antagonists; 3) FR-113452, a nearly inactive enantiomer of FK-453; and 4) KF-17837, a selective A2 receptor blocker. Adult Sprague-Dawley rats were prepared (adrenalectomized, renal denervated, uninephrectomized, and treated with indomethacin, aldosterone, and hydrocortisone) to minimize endogenous stimulation of renin release and received either vehicle (control group) or one of the four drugs. Intrarenal infusions of isoproterenol (3, 30, and 100 ng.kg-1.min-1) caused dose-related increases in plasma renin activity (PRA). This PRA response was significantly augmented in the groups receiving DPCPX (P = 0.0010) or FK-453 (P = 0.0001) but was not altered in the groups treated with FR-113452 (P = 0.3422) or KF-17837 (P = 0.2155). Systemic and renal hemodynamics and renal electrolyte excretions were monitored and could not account for the PRA augmentation caused by the A1 antagonists. This study clearly demonstrates that endogenous adenosine acts on the A1 receptor to restrain the renin release induced by activation of intrarenal beta-adrenoceptors and is not counteracted by endogenous activation of the A2 receptor.

Cytochrome C suppresses renal accumulation and nephrotoxicity of polymyxin B

2018 ◽  
Vol 38 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Z-D Li ◽  
J Luo ◽  
L-H Jia ◽  
X-Y Wang ◽  
Z-K Xun ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Polymyxin B ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
C 30 ◽  
C 50

The receptor megalin plays an important role in the accumulation of polymyxin B (PMB) in renal cells in vitro. This study aimed to examine the effects of cytochrome c (cyto c), a typical megalin ligand, on renal accumulation and nephrotoxicity of PMB in vivo. Thirty Sprague-Dawley rats were randomly divided into the vehicle control group, PMB group, PMB + cyto c 50, 100, or 200 mg/kg group, respectively, and were treated with intravenous cyto c 30 min before the administration of PMB 4.0 mg/kg once a day for consecutive 5 days. On the 4th day after administration, 24 h urine was collected to determine N-acetyl-β-D-glucosaminidase excretion. Six hours after the last injection on the 5th day, kidneys were harvested to assay PMB concentration and observe pathological alterations, and blood samples were collected to assay serum creatinine (SCr), blood urea nitrogen (BUN), and blood β2-microglobulin (β2-MG) levels. Cyto c 50, 100, and 200 mg/kg decreased the accumulation of PMB in the kidney by 18.5%, 39.1% ( p < 0.01), and 36.8% ( p < 0.01), respectively, and reduced 24 h N-acetyl-β-D- glucosaminidase excretion by 22.5% ( p < 0.05), 40.4% ( p < 0.01), and 40.4% ( p < 0.01), respectively. Kidney pathological damage induced by PMB was markedly reduced by cyto c 100 mg/kg and 200 mg/kg. However, there were no significant differences in SCr, BUN, and blood β2-MG levels among the groups. These results indicated that cyto c may inhibit the renal accumulation and nephrotoxicity of PMB in a rat model, further proving the role of megalin in the accumulation of PMB.

scholarly journals Vitamin B12 Conjugation of Peptide-YY3–36 Decreases Food Intake Compared to Native Peptide-YY3–36 Upon Subcutaneous Administration in Male Rats

Endocrinology ◽  
2015 ◽  
Vol 156 (5) ◽  
pp. 1739-1749 ◽  
Author(s):  
Kelly E. Henry ◽  
Clinton T. Elfers ◽  
Rachael M. Burke ◽  
Oleg G. Chepurny ◽  
George G. Holz ◽  
...  
Keyword(s):  
Food Intake ◽  
Vitamin B12 ◽  
Day Treatment ◽  
Subcutaneous Administration ◽  
Male Rats ◽  
Sprague Dawley ◽  
In Vivo Experiments ◽  
Sprague Dawley Rats

Challenges to peptide-based therapies include rapid clearance, ready degradation by hydrolysis/proteolysis, and poor intestinal uptake and/or a need for blood brain barrier transport. This work evaluates the efficacy of conjugation of vitamin B12 (B12) on sc administered peptide tyrosine tyrosine (PYY)3–36 function. In the current experiments, a B12-PYY3–36 conjugate was tested against native PYY3–36, and an inactive conjugate B12-PYYC36 (null control) in vitro and in vivo. In vitro experiments demonstrated similar agonism for the neuropeptide Y2 receptor by the B12-PYY3–36 conjugate (EC50 26.5 nM) compared with native PYY3–36 (EC50 16.0 nM), with the null control having an EC50 of 1.8 μM. In vivo experiments were performed in young adult male Sprague Dawley rats (9 wk). Daily treatments were delivered sc in five 1-hour pulses, each pulse delivering 5–10 nmol/kg, by implanted microinfusion pumps. Increases in hindbrain Fos expression were comparable 90 minutes after B12-PYY3–36 or PYY3–36 injection relative to saline or B12-PYYC36. Food intake was reduced during a 5-day treatment for both B12-PYY3–36- (24%, P = .001) and PYY3–36-(13%, P = .008) treated groups relative to baseline. In addition, reduction of food intake after the three dark cycle treatment pulses was more consistent with B12-PYY3–36 treatment (−26%, −29%, −27%) compared with the PYY3–36 treatment (−3%, −21%, −16%), and B12-PYY3–36 generated a significantly longer inhibition of food intake vs PYY3–36 treatment after the first two pulses (P = .041 and P = .036, respectively). These findings demonstrate a stronger, more consistent, and longer inhibition of food intake after the pulses of B12-PYY3–36 conjugate compared with the native PYY3–36.

scholarly journals In vivo model of Hirschsprung-associated enterocolitis using benzalkonium chloride

2021 ◽  
Author(s):  
Iskandar Rahardjo Budianto ◽  
Agus Firmansyah ◽  
Yefta Moenadjat ◽  
Ahmad Aulia Jusuf ◽  
Vivian Soetikno
Keyword(s):  
Sigmoid Colon ◽  
Topical Application ◽  
Benzalkonium Chloride ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Life Threatening

BACKGROUND Hirschsprung-associated enterocolitis (HAEC) is a life-threatening complication of Hirschsprung’s disease. Studies using animal models on the pathogenesis of HAEC are limited. Thus, this study aimed to establish a rat model of HAEC using topical application of 0.1% benzalkonium chloride (BAC) in the sigmoid colon. METHODS 55 male Sprague Dawley rats aged 10−12 weeks old were separated into 11 groups. The control group (n = 5) was euthanized on day-7, and the other 10 groups (n = 5 in each group) treated with 0.1% BAC in the sigmoid colon for 15 min to induce Hirschsprung’s disease were euthanized on day-7, -10, -12, -14, -17, -19, -21, -23, -25, and -28. The sigmoid colon was excised, fixed in formalin, and sectioned for histological examinations with hematoxylin and eosin staining. The degree of HAEC was compared within all groups. RESULTS Rats that were sacrificed on day-7 to -12 showed the 1st degree or early HAEC, which was most likely caused by BAC application. The 2nd degree of HAEC occurred in rats that were sacrificed on day-14 that showed a macrophage infiltration in the sigmoid colon, thus fulfilled the initial criteria for HAEC (p = 0.0025 versus control). The degree of enterocolitis increased with time, and the highest degree was found in rats that were sacrificed on day-28 (p<0.001 versus control). CONCLUSIONS Topical application of 0.1% BAC for 15 min was successfully produced HAEC model in rats, which was occurred on day-14 after the application. This model provides a useful resource for further research on the pathogenesis of HAEC.

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