scholarly journals Pharmacokinetic properties of an innovative nootropic agent based on a derivative of 3,7-diazabicyclo[3.3.1]nonane

2020 ◽  
Vol 66 (1) ◽  
pp. 71-76
Author(s):  
G.E. Brkich ◽  
N.V. Pyatigorskaya ◽  
V.V. Beregovykh ◽  
A.A. Nedorubov ◽  
O.V. Filippova ◽  
...  
Keyword(s):  
Oral Administration ◽  
Intravenous Administration ◽  
Dose Dependence ◽  
Relative Bioavailability ◽  
The Body ◽  
Male Rats ◽  
Sprague Dawley ◽  
Heterogeneous Distribution ◽  
Nootropic Agent ◽  
Distribution In Organs

The pharmacokinetics and bioavailability of a derivative of 3,7-diazabicyclo[3.3.1]nonane exhibiting a nootropic effect, were studied after a single dose to rats. The pharmacokinetics of the compound was studied after oral and intravenous administration to 270 male rats Sprague Dawley at doses of 2.5 mg/kg, 13 mg/kg and 25 mg/kg. Its distribution in organs and tissues (brain, thymus, heart, lungs, liver, kidneys, and spleen) was also investigated. It was found that after a single intravenous administration, the investigated substance was determined in the blood of animals for 24 h; the half-life was 4.69 h. The relative bioavailability of the 3,7-diazabicyclo[3.3.1]nonane derivative after oral administration was 42.3%, thus suggesting the prospect of creating dosage forms for oral administration. After a single oral administration, the dose dependence of AUC0-t was exponential. The substance is characterized by heterogeneous distribution in the body with preferential accumulation mainly in well-vascularized tissues.

Histopathological Changes of Organs (Lungs, Liver, Kidney, and Brain) After Using Two Types of AgiCoat and Acticoat Nanosilver Dressings on Deep Second-Degree Burn in Rat

2019 ◽  
Vol 41 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Hamid Karimi ◽  
Noor-Ahmad Latifi ◽  
Ali Zare Mehrjerdi ◽  
Babak Jafarnejad ◽  
Ali-Mohammad Karimi
Keyword(s):  
Wound Healing ◽  
Silver Ions ◽  
The Body ◽  
Male Rats ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Degree Burn ◽  
Significant Difference ◽  
Second Degree

Abstract Prevention of infections is a very important issue in treating the burn wounds. The nanosilver dressings have many promising advantages, but absorption of silver ions and its adverse effects to the body were always a question. The aim of this study was to compare Silver serum levels and acute toxic effects of nanosilver on histopathology of organs (lungs, liver, kidney, spleen, and brain) in two types of AgiCoat and Acticoat (nanosilver) dressings on second-degree deep burn in rat. This is an experimental study conducted in our animal laboratory. We divided 24 Sprague–Dawley male rats weighing 300 to 350 randomly into two groups. After anesthesia, a second deep-degree burn was made over dorsal skins of rats by standard method. For group A, Agicoat and, for group B, Acticoat dressings were used. The dressings were changed every 3 days with AgiCoat and Acticoat, respectively. After 14 days, we got blood samples and tissue samples taken from heart, liver, kidneys, spleen, lungs, and brain and a sample from dorsal skin of the rat for histopathological examinations. The results showed that the levels of serum silver in both groups were significantly higher than the standard level (1.22 part per million (PM); AgiCoat, P = .017; Acticoat, P = .000), but there was no significant difference between the groups (P = .551). Examination of the relationship between the level of serum silver and histopathological changes in liver showed that hepatotoxicity of AgiCoat was higher compared with Acticoat and the difference was significant (P = .002). There were no pathological changes in brain, kidneys, spleen, heart, and lungs. Wound healing was faster in Acticoat group. The nanosilver dressings can cause toxicity in liver but not in kidney, brain, spleen, heart, and lungs. Liver pathology and hepatotoxicity were more prominent in AgiCoat group. Wound healing was faster in Acticoat group.

scholarly journals PHARMACOKINETICS AND BIOAVAILABILITY OF ORTHOSIPHON STAMINEUS ETHANOLIC EXTRACT AND ITS-NANO LIPOSOMES IN SPRAGUE-DAWLEY RATS

2016 ◽  
Vol 9 (1) ◽  
pp. 199 ◽  
Author(s):  
Armaghan Shafaei ◽  
Mohammed Ali Ahmed Saeed ◽  
Abdalrahim F. A. Aisha ◽  
Zhari Ismail
Keyword(s):  
Intravenous Administration ◽  
High Performance ◽  
Volume Ratio ◽  
Ethanolic Extract ◽  
Pharmacokinetic Profile ◽  
The Body ◽  
Internal Diameter ◽  
Sprague Dawley ◽  
Orthosiphon Stamineus ◽  
Marker Compounds

<p><strong>Objective: </strong>This study aimed to perform pharmacokinetic profile of rosmarinic acid (RA), sinensitin (SIN), eupatorin (EUP) and 3<sup>΄</sup>-hydroxy-5,6,7,4΄-tetramethoxyflavone (TMF) in <em>Orthosiphon stamineus</em> ethanolic extract (OS-E) and its nanoliposomes (OS-EL) after oral and intravenous administration in Sprague-Dawley rat’s plasma by developing and validating a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection.</p><p><strong>Methods: </strong>An isocratic elution program consisting of methanol: tetrahydrofuran: water (0.1% H<sub>3</sub>PO<sub>4</sub>) mixture in the volume ratio 55: 5: 40 on Nucleosil C18 column (250 × 4.6 mm internal diameter × 5 µm particles size) was applied. The current study followed a two-ways crossover study design. OS-E and OS-EL were administered orally at 1000 and 500 mg/kg, respectively. They were also administered intravenously at 250 mg/kg via the tail vein.</p><p><strong>Results</strong>:<strong> </strong>The HPLC-UV method was successfully developed and validated for simultaneous determination of major chemical constituent from OS-E and OS-EL in rat’s plasma. The method recorded the mean recoveries from extraction were between 91.39 and 100.32%. With regards to the intravenous administration of OS-EL, all four marker compounds appeared to be poorly distributed and cleared slowly from the body compared to OS-E. Whilst in oral administration of OS-EL, the bioavailability of all marker compounds were higher than OS-E due to higher solubility of encapsulation in phospholipids.</p><p><strong>Conclusion</strong>:<strong> </strong>The higher solubility and bioavailability of OS-EL may contribute to encapsulation in phospholipids.</p>

312 An Evaluation of the Clinical and Histological Effects of High Dose Radiosurgery on the Rat Dorsal Root Ganglion

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 266-267
Author(s):  
Ezequiel Goldschmidt ◽  
Wendy Fellows-Mayle ◽  
Erin Paschel ◽  
Ajay Niranjan ◽  
John Flickinger ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
The Body ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Histopathological Response ◽  
Histological Techniques ◽  
Sensory Deficits ◽  
The Right

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is a safe and effective technique to create lesions of the brain and trigeminal nerve (TGN) in order to achieve neuromodulation. The lumbar dorsal root ganglion (DRG) contains the body of the sensory neurons responsible for pain sensitivity and can be targeted to treat chronic and debilitating pain in the extremities. Neuromodulation of the DRG might therefore improve chronic peripheral pain. This study was performed to determine the feasibility as well as clinical and histological effects of delivering high dose SRS targeted to the lumbar DRG in a rat model. METHODS Four Sprague Dawley male rats underwent 80 Gy maximum dose single-fraction SRS to the left L5 and L6 DRG using the Leksell Gamma Knife Icon (Elekta, Atlanta, GA) with onboard cone-beam CT imaging using 4 mm diameter collimators. The right L5 and L6 DRGs served as the controls. The animals were evaluated for motor and sensory deficits every two weeks. Two animals were sacrificed at 3 and two at 6 months after SRS. The lumbar spines were harvested and decalcified. Common histological techniques (Masson trichrome, Prussian blue) were used to assess for fibrosis and demyelination. RESULTS >No detectable motor or sensory deficits were seen in any animal. Histological changes including fibrosis and loss of myelin were noted to the left L5 and L6 DRGs, but not the right side control DRGs. Fibrotic changes within the vertebral body were also evident on the treated sides of the vertebral bodies. CONCLUSION We were able to detect a demyelinating histopathological response from SRS delivered to the DRG in rats. Since such changes mimic those seen after trigeminal SRS in experimental animals, we hypothesize that radiosurgery may be a potential option in chronic spinal radicular pain amenable to neuromodulation.

scholarly journals Antiobesity Effect ofCodonopsis lanceolatain High-Calorie/High-Fat-Diet-Induced Obese Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hye-Kyung Choi ◽  
Eun-Kyung Won ◽  
Young Pyo Jang ◽  
Se-Young Choung
Keyword(s):  
Lipid Accumulation ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Normal Diet ◽  
The Body ◽  
Male Rats ◽  
Sprague Dawley ◽  
High Fat ◽  
Codonopsis Lanceolata ◽  
High Calorie

The antiobesity effects ofCodonopsis lanceolata(CL) were evaluated in a high-calorie/high-fat-diet (HFD-) induced obesity rat model and 3T3-L1 cells. The Sprague-Dawley male rats were fed a normal diet (ND) or a HFD for a period of 12 weeks. The rats were subdivided into groups: ND, ND + wildCodonopsis lanceolata(wCL) (900 mg/kg/day, p.o.), ND + cultivatedCodonopsis lanceolata(cCL) (900 mg/kg/day, p.o.), HFD, HFD + wCL (100, 300, or 900 mg/kg/day, p.o.), HFD + cCL (100, 300, or 900 mg/kg/day, p.o.), and HFD + sibutramine. The body weight gains of the administered HFD + CL (wCL or CCL) were lower than those of the rats fed with only the HFD group. Moreover, the weight of adipose pads and the serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol in the group administered HDL + CL were significantly lower than in the HFD group. The inhibitory effect of lipid accumulation in 3T3-L1 cells was measured by Oil Red O staining and reverse transcription-polymerase chain reaction (RT-PCR). Treatment of 3T3-L1 cells with wCL inhibited lipid accumulation and expression of C/EBPαand PPARγ. These results suggest that CL has a great potential as a functional food with anti-obesity effects and as a therapeutic alternative in the treatment of obesity.

Defense of body weight against chronic caloric restriction in obesity-prone and -resistant rats

2000 ◽  
Vol 278 (1) ◽  
pp. R231-R237 ◽  
Author(s):  
Barry E. Levin ◽  
Ambrose A. Dunn-Meynell
Keyword(s):  
Caloric Restriction ◽  
High Energy ◽  
The Body ◽  
Male Rats ◽  
Sprague Dawley ◽  
Insulin Levels ◽  
Sprague Dawley Rats ◽  
Body Weights ◽  
Plasma Leptin ◽  
Adipose Mass

Half of Sprague-Dawley rats develop and defend diet-induced obesity (DIO) or diet resistance (DR) when fed a high-energy (HE) diet. Here, adult male rats were made DIO or DR after 10 wk on HE diet. Then half of each group was food restricted for 8 wk on chow to maintain their body weights at 90% of their respective baselines. Rate and magnitude of weight loss were comparable, but maintenance energy intake and the degree of sympathetic activity (24-h urine norepinephrine) inhibition were 17 and 29% lower, respectively, in restricted DR than DIO rats. Restricted DIO rats reduced adipose depot weights, plasma leptin, and insulin levels by 35%. Restricted DR rats reduced none of these. When fed ad libitum, both DR and DIO rats returned to the body weights of their respective chow-fed phenotype controls within 2 wk. This was associated with increased adipose mass and leptin and insulin levels only in DIO rats. Thus DR rats appear to alter primarily their lean body mass, whereas DIO rats primarily alter their adipose mass during chronic caloric restriction and refeeding.

scholarly journals Pharmacokinetic Interaction Between Oltipraz and Silymarin in Rats

2009 ◽  
Vol 12 (1) ◽  
pp. 1 ◽  
Author(s):  
Min Kyung Kang ◽  
Soo Kyung Bae ◽  
Jin Wan Kim ◽  
Myung Gull Lee
Keyword(s):  
Oral Administration ◽  
Intravenous Administration ◽  
Pharmacokinetic Interaction ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Intravenous And Oral Administration ◽  
Single Intravenous Administration

ABSTRACT. Purpose: To evaluate the pharmacokinetic interaction between oltipraz and silymarin after intravenous and oral administration of both drugs to male Sprague–Dawley rats. Methods: Oltipraz (single doses of 10 and 30 mg/kg for intravenous and oral administration, respectively), silymarin (single doses of 50 and 100 mg/kg for intravenous and oral administration, respectively, and 14 days oral administration of 100 mg/kg), alone and together were administered to control rats. Results: The pharmacokinetic parameters of oltipraz did not significantly altered by silymarin. However, after intravenous administration of the drugs together, the AUCs of unconjugated, conjugated, and total (unconjugated plus conjugated) silibinin were significantly different (32.7% decrease, and 32.1% and 27.2% increase, respectively), and total and (CL) and non-renal (CLNR ) clearance of unconjugated silibinin were significantly faster (49.4% and 61.1% increase, respectively) than those of silymarin alone (without oltipraz). After oral administration of silymarin with or without oltipraz, however, the pharmacokinetic parameters of unconjugated, conjugated, and total silibinin were comparable. Conclusions: After single intravenous administration of the drugs together, the AUC of unconjugated silibinin was significantly smaller, but that of both conjugated and total silibinin was significantly greater. This could have been due to an increase in the formation of conjugates (glucuronidation and sulfation) of silibinin as induced by oltipraz. After simultaneous oral administration of the drugs, however, the AUCs (or AUC0−12 h) of unconjugated, conjugated, and total silibinin were comparable.

scholarly journals Circadian variability of body temperature responses to methamphetamine

2018 ◽  
Vol 314 (1) ◽  
pp. R43-R48 ◽  
Author(s):  
Abolhassan Behrouzvaziri ◽  
Maria V. Zaretskaia ◽  
Daniel E. Rusyniak ◽  
Dmitry V. Zaretsky ◽  
Yaroslav I. Molkov
Keyword(s):  
Body Temperature ◽  
Dose Dependence ◽  
The Body ◽  
Sprague Dawley ◽  
Baseline Activity ◽  
Sprague Dawley Rats ◽  
Excitatory Component ◽  
Hyperthermic Response ◽  
Living Organisms ◽  
Temperature Responses

Vital parameters of living organisms exhibit circadian rhythmicity. Although rats are nocturnal animals, most of the studies involving rats are performed during the day. The objective of this study was to examine the circadian variability of the body temperature responses to methamphetamine. Body temperature was recorded in male Sprague-Dawley rats that received intraperitoneal injections of methamphetamine (Meth, 1 or 5 mg/kg) or saline at 10 AM or at 10 PM. The baseline body temperature at night was 0.8°C higher than during the day. Both during the day and at night, 1 mg/kg of Meth induced monophasic hyperthermia. However, the maximal temperature increase at night was 50% smaller than during the daytime. Injection of 5 mg/kg of Meth during the daytime caused a delayed hyperthermic response. In contrast, the same dose at night produced responses with a tendency toward a decrease of body temperature. Using mathematical modeling, we previously showed that the complex dose dependence of the daytime temperature responses to Meth results from an interplay between inhibitory and excitatory drives. In this study, using our model, we explain the suppression of the hyperthermia in response to Meth at night. First, we found that the baseline activity of the excitatory drive is greater at night. It appears partially saturated and thus is additionally activated by Meth to a lesser extent. Therefore, the excitatory component causes less hyperthermia or becomes overpowered by the inhibitory drive in response to the higher dose. Second, at night the injection of Meth results in reduction of the equilibrium body temperature, leading to gradual cooling counteracting hyperthermia.

scholarly journals Effect of Ticagrelor, a Cytochrome P450 3A4 Inhibitor, on the Pharmacokinetics of Tadalafil in Rats

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 354 ◽  
Author(s):  
Young-Guk Na ◽  
Jin-Ju Byeon ◽  
Hyun Wook Huh ◽  
Min-Ki Kim ◽  
Young G. Shin ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Oral Administration ◽  
Systemic Exposure ◽  
Compartment Model ◽  
Male Rats ◽  
Combination Regimen ◽  
Sprague Dawley ◽  
Pharmacokinetic Properties ◽  
Pretreated Group ◽  
Few Data

Tadalafil is a cytochrome P450 (CYP) 3A4 substrate. Because there are few data on drug-drug interactions, it is advisable to take sufficient consideration when co-administering tadalafil with CYP3A4 inducers or inhibitors. This study was conducted to assess the effect of ticagrelor, a CYP3A4 inhibitor, on the pharmacokinetic properties of tadalafil after oral administration to rats. A total of 20 Sprague–Dawley male rats were randomly divided into the non-pretreated group and ticagrelor-pretreated group, and tadalafil was orally administered to each group after pretreatment with or without ticagrelor. Blood samples were collected at predetermined time points after oral administration of tadalafil. As a result, systemic exposure of tadalafil in the ticagrelor-pretreated group was significantly increased compared to the non-pretreated group (1.61-fold), and the clearance of tadalafil in the ticagrelor-pretreated group was significantly reduced than the non-pretreated group (37%). The prediction of the drug profile through the one-compartment model could explain the differences of pharmacokinetic properties of tadalafil in the non-pretreated and ticagrelor-pretreated groups. This study suggests that ticagrelor reduces a CYP3A-mediated tadalafil metabolism and that tadalafil and a combination regimen with tadalafil and ticagrelor requires dose control and specific pharmacotherapy.

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