Long-Term Effects of Panax Ginseng on Disposition of Fexofenadine in Rats in vivo

2009 ◽  
Vol 37 (04) ◽  
pp. 657-667 ◽  
Author(s):  
Ruhong Zhang ◽  
Jinjie Jie ◽  
Yan'an Zhou ◽  
Zhijian Cao ◽  
Wenxin Li
Keyword(s):  
Oral Dose ◽  
Panax Ginseng ◽  
Area Under The Curve ◽  
Pharmacokinetic Interaction ◽  
Male Rats ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Long Term Effects

This study was designed to explore the pharmacokinetic interaction of Panax Ginseng with fexofenadine in rats. Sprague-Dawley (SD) male rats were divided randomly into four groups: control oral and treatment oral dose groups ( n = 6, respectively); control intravenous and treatment intravenous dose groups ( n = 5, respectively). A single dose of fexofenadine (10 mg/kg for intravenous group rats and 100 mg/kg for oral dose group rats) was administered after 14 consecutive days of gastric gavage feeding of panax ginseng suspension (150 mg/kg/day) to treatment groups while the same volume of vehicle (1.6% ethanol) was administered as placebo to control groups. Blood samples were collected from 0 to 12 hours and levels of fexofenadine were measured by LC-MS/MS. Tissues were harvested to determine tissue/blood ratios. The pharmacokinetic parameters of fexofenadine were calculated using non-compartmental analysis. In the oral dose groups, (extravenous) panax ginseng decreased the area under the curve between 0–12 hours (AUC0–12) from 102490.7 ± 25273.5 to 49933.3 ± 12072.9 min*ng/ml ( p < 0.005), decreased C max from 1102.0 ± 116.6 to 274.3 ± 180.6 ng/ml ( p < 0.001), and significantly decreased ratios of brain to plasma concentration (B/P) ( p < 0.05). In the intravenous groups, panax ginseng only reduced B/P ratios ( p < 0.05). The mean bioavailability ( F ev ) of fexofenadine was decreased by 16.1% in the extravenous dose treatment group ( p < 0.05). Long term administration of panax ginseng to rats might induce both intestinal and brain endothelium p-glycoprotein (p-gp) expression. In addition, long term use of panax ginseng reduced the bioavailability of concurrently administered fexofenadine.

scholarly journals Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir following Intravenous and Oral Administrations in Rats: A study Involving in vivo corneal Uptake of Acyclovir following Oral Dosing

2009 ◽  
Vol 1 ◽  
pp. OED.S2857 ◽  
Author(s):  
Ravi S. Talluri ◽  
Ripal Gaudana ◽  
Sudharshan Hariharan ◽  
Ashim K. Mitra
Keyword(s):  
Oral Administration ◽  
Oral Absorption ◽  
Area Under The Curve ◽  
Systemic Circulation ◽  
Precipitation Method ◽  
Drug Candidate ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Uptake Studies

Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV) in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV), L-valine-D-valine-acyclovir (LDACV) and D-valine-L-valine acyclovir (DLACV) prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC) in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. Cmax (μM) and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

Testicular oxytocin: effects of intratesticular oxytocin in the rat

1991 ◽  
Vol 130 (2) ◽  
pp. 231-NP ◽  
Author(s):  
H. D. Nicholson ◽  
S. E. F. Guldenaar ◽  
G. J. Boer ◽  
B. T. Pickering
Keyword(s):  
Leydig Cells ◽  
Light And Electron Microscopy ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Epididymal Sperm ◽  
Long Term Effects ◽  
Sperm Counts ◽  
Term Administration

ABSTRACT The long-term effects of oxytocin administration on the testis were studied using intratesticular implants. Adult male rats had an Accurel device containing 20 μg oxytocin (releasing approximately 200 ng/day) implanted into the parenchyma of each testis; control animals received empty devices. The animals were killed at weekly intervals for 4 weeks. Some animals were perfused and the testes processed for light and electron microscopy. Blood was collected from the remaining animals for the measurement of testosterone, dihydrotestosterone, LH, FSH and oxytocin; epididymal sperm counts were measured and the testes were extracted and radioimmunoassayed for testosterone, dihydrotestosterone and oxytocin. Long-term administration of oxytocin resulted in a significant reduction in testicular and plasma testosterone levels throughout the 4-week period examined and, after 14 days of treatment, lipid droplets were seen in the Leydig cells of treated but not control animals. Concentrations of dihydrotestosterone in the plasma and testes of the oxytocin-treated animals, however, were significantly elevated after 7 and 14 days and at no time fell below control values. Plasma FSH levels were also lower in the oxytocin-treated animals. Intratesticular oxytocin treatment did not affect LH or oxytocin concentrations in the plasma, epididymal sperm counts or the number of Leydig cells in the testis. Empty Accurel devices had no effect on testicular morphology. This study provides the first evidence that oxytocin in vivo can modify steroidogenesis in the testis. Journal of Endocrinology (1991) 130, 231–238

scholarly journals In vivo Activity of Dust Inhalation at Ratcon Quarry, Sokuro Village, Oluyole, Ibadan Oyo State

2021 ◽  
pp. 9-15
Author(s):  
Adeniyi Abayomi Olusegun
Keyword(s):  
Interstitial Pneumonia ◽  
Exposure Time ◽  
Male Rats ◽  
Human Beings ◽  
Long Term Effects ◽  
Air Concentration ◽  
Dust Inhalation ◽  
Average Body

A total of twenty (20) experimental adult male rats, aged 60 days (7 to 8 weeks) with average body weight between 150-200 gm were grouped, restrained inside laboratory approved plastic holders and exposed to dust inhalation at the quarry site with exposure time of 7, 14 and 21 days to reflect short-term effects while 42days represent long-term effects of dust inhalation on human beings. Each specimen was collected and sacrificed at their grouped survival periods and subjected to laboratory analysis that include Hematology and Histopathology of the lungs. The Hematologyresults of the 7 and 14days specimens revealed no remarkable changes in the Erythrogram (PCV, HB and RBC), the Leucogram (WBC) and the Platelets but however, the results of the 21 and 42 days specimen revealed leukocytosis (increase in WBC), lymphocytosis (increase Lym) and neutrophilia (increase neutrophils) (p<0.05). The Histopathology results of the first specimen (7 days exposure) showed no observable lesion, the second specimen(14 days) showed capillary congestion and mild interstitial pneumonia, while the third (21 days) and fourth (42 days) samples showed the rats graduating from mild to moderate interstitial pneumonia and oedema. The risk of these diseases depends on the amount of organic or inorganic dusts inhaled and deposited in the alveolar region, the air concentration of respirable dust as well as the exposure time and breathing pattern.

scholarly journals EFFECT OF 70% ETHANOL EXTRACT OF ORTHOSIPHONIS STAMINEUS BENTH LEAVES ON THE PHARMACOKINETIC PARAMETERS OF FUROSEMIDE IN MALE WHITE RATS

2017 ◽  
Vol 9 ◽  
pp. 54
Author(s):  
Riana Maya Oktaviani ◽  
Santi Purna Sari ◽  
Yahdiana Harahap
Keyword(s):  
White Male ◽  
Area Under The Curve ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Male Rats ◽  
Combination Group ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
White Rats

Objective: This study aimed to observe the effect of the 70% ethanol extract of Orthosiphonis stamineus Benth leaves on the pharmacokineticparameters of furosemide in white male rats.Methods: 18 Sprague–Dawley male rats were divided into three groups: The normal control group was given only 1% carboxymethyl cellulose,the furosemide group was given 7.2 mg/200 g body weight (BW) suspension of furosemide, and the combination group was given 700 mg/kg BWsuspension of the 70% ethanolic extract of O. stamineus Benth leaves for 4 days followed by a 7.2 mg/200 g BW suspension of furosemide. On the4th day of treatment, we performed orbital sinus blood sampling on the eyes of the rats and analyzed the levels of furosemide in plasma using highperformanceliquid chromatography.Results: Therefore, the results showed that the administration of the 70% ethanol extract of O. stamineus Benth leaves improves the pharmacokineticparameters of furosemide on Cpmax and the area under the curve (p<0.05).Conclusion: This study concludes that the 70% ethanol extract of O. stamineus Benth leaves improves the pharmacokinetic parameters of furosemidein white male rats.

scholarly journals The long-term bio-behavioural effects of juvenile sildenafil treatment in Sprague-Dawley versus Flinders Sensitive Line rats

2021 ◽  
pp. 1-20
Author(s):  
Juandré Lambertus Bernardus Saayman ◽  
Stephanus Frederik Steyn ◽  
Christiaan Beyers Brink
Keyword(s):  
Sprague Dawley ◽  
Long Term Effects ◽  
Bdnf Level ◽  
Treatment Groups ◽  
Sd Rats ◽  
Behavioural Effects ◽  
Sensitive Line ◽  
Level Analysis ◽  
Flinders Sensitive Line

Abstract Objective: To investigate the long-term effects of juvenile sub-chronic sildenafil (SIL) treatment on the depressive-like behaviour and hippocampal brain-derived neurotrophic factor (BDNF) levels of adult Sprague-Dawley (SD) versus Flinders Sensitive Line (FSL) rats. Methods: SD and FSL rats were divided into pre-pubertal and pubertal groups, whereafter 14-day saline or SIL treatment was initiated. Pre-pubertal and pubertal rats were treated from postnatal day 21 (PND21) and PND35, respectively. The open field and forced swim tests (FST) were performed on PND60, followed by hippocampal BDNF level analysis one day later. Results: FSL rats displayed greater immobility in the FST compared to SD rats (p < 0.0001), which was reduced by SIL (p < 0.0001), regardless of treatment period. Hippocampal BDNF levels were unaltered by SIL in all treatment groups (p > 0.05). Conclusion: Juvenile sub-chronic SIL treatment reduces the risk of depressive-like behaviour manifesting during young adulthood in genetically susceptible rats.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

scholarly journals Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons

2014 ◽  
Vol 306 (2) ◽  
pp. L170-L182 ◽  
Author(s):  
Anna A. Shvedova ◽  
Naveena Yanamala ◽  
Elena R. Kisin ◽  
Alexey V. Tkach ◽  
Ashley R. Murray ◽  
...  
Keyword(s):  
Lung Tumor ◽  
Inhalation Exposure ◽  
Geometric Feature ◽  
Width Ratio ◽  
Long Term Effects ◽  
Genotoxic Effects ◽  
Pulmonary Exposure ◽  
Pharyngeal Aspiration

The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF), high length to width ratio, makes them similar to a hazardous agent, asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here, we compared inflammatory, fibrogenic, and genotoxic effects of CNF, SWCNT, or asbestos in mice 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that these particles can be visualized in the lung at 1 yr postexposure, whereas some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic, and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K-ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 yr postexposure to SWCNT, CNF, and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF, and asbestos is defined, not only by their chemical composition, but also by the specific surface area and type of exposure.

scholarly journals Bone Regeneration Capacity of Newly Developed Uncalcined/Unsintered Hydroxyapatite and Poly-l-lactide-co-glycolide Sheet in Maxillofacial Surgery: An In Vivo Study

Nanomaterials ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 22
Author(s):  
Huy Xuan Ngo ◽  
Quang Ngoc Dong ◽  
Yunpeng Bai ◽  
Jingjing Sha ◽  
Shinji Ishizuka ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Reconstructive Surgery ◽  
Early Stage ◽  
Maxillofacial Surgery ◽  
Male Rats ◽  
Regeneration Ability ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Rat Mandible

Uncalcined/unsintered hydroxyapatite and poly-l-lactide-co-glycolide (u-HA/PLLA/PGA) is a new bioresorbable nanomaterial with superior characteristics compared with current bioresorbable materials, including appropriate mechanical properties, outstanding bioactive/osteoconductive features, and remarkably shorter resorption time. Nevertheless, the bone regeneration characteristics of this nanomaterial have not been evaluated in maxillofacial reconstructive surgery. In this study, we used a rat mandible model to assess the bone regeneration ability of u-HA/PLLA/PGA material, compared with uncalcined/unsintered hydroxyapatite and poly-l-lactide acid (u-HA/PLLA) material, which has demonstrated excellent bone regenerative ability. A 4-mm-diameter defect was created at the mandibular angle area in 28 Sprague Dawley male rats. The rats were divided into three groups: u-HA/PLLA/PGA (u-HA/PLLA/PGA graft + defect), u-HA/PLLA (u-HA/PLLA graft + defect), and sham control (defect alone). At 1, 3, 8, and 16 weeks after surgeries, the rats were sacrificed and assessed by micro-computed tomography, histological analysis with hematoxylin and eosin staining, and immunohistochemical analyses. The results confirmed that the accelerated bone bioactive/regenerative osteoconduction of u-HA/PLLA/PGA was comparable with that of u-HA/PLLA in the rat mandible model. Furthermore, this new regenerative nanomaterial was able to more rapidly induce bone formation in the early stage and had great potential for further clinical applications in maxillofacial reconstructive surgery.

scholarly journals Pharmacokinetics of α-Pyrrolidinovalerophenone in Male Rats with and without Vaccination with an α-Pyrrolidinovalerophenone Vaccine

2021 ◽  
Vol 24 ◽  
pp. 267-276
Author(s):  
Samantha McClenahan ◽  
Melinda Gunnell ◽  
Michael Owens
Keyword(s):  
Treatment Time ◽  
Area Under The Curve ◽  
Early Time ◽  
Volume Of Distribution ◽  
Male Rats ◽  
Serum Concentrations ◽  
Sprague Dawley ◽  
Serum Samples ◽  
Maximum Serum ◽  
The Brain

PURPOSE: α-Pyrrolidinovalerophenone (α-PVP) is a second-generation synthetic cathinone which acts as an inhibitor at the dopamine and norepinephrine transporters in the brain. These novel studies determined the pharmacokinetics (PK) of α-PVP in rats and then evaluated the effects of an α-PVP vaccine on the PK profile. METHODS: Adult male Sprague-Dawley rats were randomly divided into treatment groups (n = 24/group) in which the vaccinated rats received an initial and two booster immunizations of the α-PVP vaccine at 0, 3, and 9 wks. Control rats received saline injections. α-PVP (0.56, 1, 3 mg/kg, sc) was then administered to both groups between 11-12 weeks and serum samples were collected for determination of α-PVP serum concentrations by LC-MS/MS (n=6 rats/treatment/time). At 13 weeks, brain, heart and kidney concentrations of α-PVP were determined by LC-MS/MS after administration of 1 mg/kg α-PVP (n=4-5 rats/treatment/time). RESULTS: PK values in control rats showed dose-dependent increases in maximum serum concentrations (Cmax) and area under the curve (AUCinf) values with an elimination half-life (t1/2) of approximately 2.1 h. α-PVP exhibited linear PK profile in control rats. Vaccinated rats had significantly (p<0.05) higher serum Cmax and AUCinf values than controls, and significantly reduced total body clearance, volume of distribution and t1/2 values. Vaccinated rats had significantly lower α-PVP concentrations in the brain, heart, and kidney in comparison to control rats at early time points. CONCLUSION: Vaccination with the novel α-PVP vaccine significantly altered serum PK leading to a time-dependent reduction in brain, kidney and heart concentrations of α-PVP compared to controls.

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