scholarly journals Evaluation of the Influence of Zhenwu Tang on the Pharmacokinetics of Digoxin in Rats Using HPLC-MS/MS

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Chao Li ◽  
Dahu Liang ◽  
Yanhao Liu ◽  
Chaozhuang Shen ◽  
Xiaohu Wang ◽  
...  
Keyword(s):  
Deionized Water ◽  
Therapeutic Window ◽  
Sprague Dawley ◽  
Glycoprotein P ◽  
Active Efflux ◽  
Time Points ◽  
Sprague Dawley Rats ◽  
Combined Use ◽  
Positive Inotropic Drug ◽  
Excised Tissues

Digoxin (DIG) is a positive inotropic drug with a narrow therapeutic window that is used in the clinic for heart failure. The active efflux transporter of DIG, P-glycoprotein (P-gp), mediates DIG absorption and excretion in rats and humans. Up to date, several studies have shown that the ginger and Poria extracts in Zhenwu Tang (ZWT) affect P-gp transport activity. This study aimed to explore the effects of ZWT on the tissue distribution and pharmacokinetics of DIG in rats. The deionized water or ZWT (18.75 g/kg) was orally administered to male Sprague–Dawley rats once a day for 14 days as a pretreatment. On day 15, 1 hour after receiving deionized water or ZWT, the rats were given the solution of DIG at 0.045 mg/kg dose, and the collection of blood samples was carried out from the fundus vein or excised tissues at various time points. HPLC-MS/MS was used for the determination of the DIG concentrations in the plasma and the tissues under investigation. The pharmacokinetic interactions between DIG and ZWT after oral coadministration in rats revealed significant reductions in DIG Cmax and AUC0-∞, as well as significant increases in T1/2 and MRT0-∞. When coadministered with ZWT, the DIG concentration in four of the investigated tissues statistically decreased at different time points except for the stomach. This study found that combining DIG with ZWT reduced not only DIG plasma exposure but also DIG accumulation in tissues (heart, liver, lungs, and kidneys). The findings of our study could help to improve the drug's validity and safety in clinical applications and provide a pharmacological basis for the combined use of DIG and ZWT.

scholarly journals Different Influences on Tacrolimus Pharmacokinetics by Coadministrations of Zhi Ke and Zhi Shi in Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Shiuan-Pey Lin ◽  
Ping-Ping Wu ◽  
Yu-Chi Hou ◽  
Shang-Yuan Tsai ◽  
Meng-Ju Wang ◽  
...  
Keyword(s):  
Cell Line ◽  
Therapeutic Window ◽  
Blood Levels ◽  
Sprague Dawley ◽  
Glycoprotein P ◽  
Transplant Patients ◽  
Sprague Dawley Rats ◽  
Microparticle Enzyme Immunoassay ◽  
Mechanism Of Interaction ◽  
Tacrolimus Pharmacokinetics

Tacrolimus, an immunosuppressant with narrow therapeutic window, has been used widely in transplant patients. Grapefruit juice and pomelo have been reported to increase the blood levels of tacrolimus. Zhi Ke and Zhi Shi, the ripe peels and unripe fruits ofCitrus aurantiumwhich is chemotaxonomically related to grapefruit and pomelo, are in wide use in clinical Chinese medicine. To investigate the possible interaction of these twoCitrusherbs with tacrolimus, male Sprague-Dawley rats were orally given tacrolimus (1.5 mg/kg) with and without Zhi Ke and Zhi Shi decoctions in a cross-over design. Blood samples were withdrawn via cardiopuncture at specific time and quantitated by a microparticle enzyme immunoassay. In addition, to explore the mechanism of interaction, LS 180 cell line was used for the transport study of rhodamine 123, a typical substrate of P-glycoprotein (P-gp). The results showed that Zhi Shi significantly decreased theCmax⁡andAUC0-tof tacrolimus by 72.4% and 72.0%, respectively, whereas Zhi Ke did not affect tacrolimus pharmacokinetics. LS 180 cell line study indicated that Zhi Shi increased the efflux activity of P-gp, enabling us to explain the decreased oral bioavailability of tacrolimus caused by Zhi Shi. Hence, we suggest that Zhi Shi be contraindicated for transplant patients treated with tacrolimus to reduce the risk of allograft rejection.

scholarly journals N-Acetylcysteine Added to Local Anesthesia Reduces Scar Area and Width in Early Wound Healing—An Animal Model Study

2021 ◽  
Vol 22 (14) ◽  
pp. 7549
Author(s):  
Wiktor Paskal ◽  
Adriana M. Paskal ◽  
Piotr Pietruski ◽  
Albert Stachura ◽  
Kacper Pełka ◽  
...  
Keyword(s):  
Wound Healing ◽  
Early Stage ◽  
Healing Process ◽  
Wound Healing Process ◽  
Sprague Dawley ◽  
Time Points ◽  
Model Study ◽  
Sprague Dawley Rats ◽  
Animal Model Study ◽  
Anesthetic Solution

The aim of the study was to evaluate if a pre-incisional N-acetylcysteine (NAC) treatment altered the process of wound healing in a rat model. The dorsal skin of 24 Sprague-Dawley rats was incised in six locations. Before the incisions were made, skin was injected either with lidocaine and epinephrine (one side) or with these agents supplemented with 0.015%, 0.03%, or 0.045% NAC (contralaterally). Photographic documentation of the wound healing process was made at 11 time points. Rats were sacrificed 3, 7, 14, or 60 days after incision to excise scars for histological analysis. They included: Abramov scale scoring, histomorphometry analysis, and collagen fiber arrangement assessment. Skin pretreated with 0.03% NAC produced the shortest scars at all analyzed time points, though this result was statistically insignificant. At this NAC concentration the scars had smaller areas on the third day and were narrower on the day 4 compared with all the other groups (p < 0.05). On day 7, at the same concentration of NAC, the scars had a higher superficial concentration index (p = 0.03) and larger dermal proliferation area (p = 0.04). NAC addition to pre-incisional anesthetic solution decreased wound size and width at an early stage of scar formation at all concentrations; however, with optimal results at 0.03% concentration.

Effect of caloric content and composition of a liquid meal on gastric emptying in the rat

1994 ◽  
Vol 267 (5) ◽  
pp. R1163-R1167 ◽  
Author(s):  
L. L. Maerz ◽  
H. Sankaran ◽  
S. J. Scharpf ◽  
C. W. Deveney
Keyword(s):  
Gastric Emptying ◽  
Gamma Camera ◽  
Casein Hydrolysate ◽  
Caloric Content ◽  
Diethylenetriaminepentaacetic Acid ◽  
Sprague Dawley ◽  
Substrate Composition ◽  
Liquid Meal ◽  
Time Points ◽  
Sprague Dawley Rats

We examined the effect of caloric content and substrate composition on gastric emptying in conscious Sprague-Dawley rats using gastric radioscintigraphy. Three-milliliter volumes of normal saline, glucose, casein hydrolysate, or intralipid containing 0, 1, 2, 3, or 6 kcal labeled with 99mTc-diethylenetriaminepentaacetic acid were given intragastrically. Gamma-camera imaging and computer analysis allowed construction of gastric emptying curves constructed over many time points for each emptying study. There was no difference in the half-emptying times (t1/2) between different substrates with equal calories, and increasing calories significantly prolonged gastric emptying for all substrates. Emptying occurred in a linear fashion with meals containing calories. With 3-ml meals containing 2, 3, or 6 kcal, the rate of delivery of calories to the duodenum is constant regardless of substrate or change in caloric content. We conclude that the rate of caloric delivery to the small intestine with gastric infusion of 1-6 kcal is relatively constant despite differences in total caloric load, substrate composition, and osmolarity.

scholarly journals The importance of aminoguanidine and methylprednisolone administration in lung contusion after chest trauma

2021 ◽  
Vol 38 (4) ◽  
pp. 504-510
Author(s):  
Fatih ÇALIŞKAN ◽  
Hızır Ufuk AKDEMİR ◽  
Celal KATI ◽  
Latif DURAN ◽  
Tolga GÜVENÇ
Keyword(s):  
Combined Treatment ◽  
Serum Levels ◽  
The Other ◽  
Pulmonary Contusion ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Combined Use ◽  
Significant Difference ◽  
All Treatment

This study aims to evaluate the effect of the antioxidant and anti-inflammatory properties of aminoguanidine and metylprednisolone (MP) on lung tissue in a pulmonary contusion model of rats and evaluate whether their combined use improves treatment efficacy. This study included 35 female Sprague Dawley rats weighing 250-300 grams. The rats were divided into five groups as following: Sham; Pulmonary Contusion (PC); PC+MP, PC group treated with i.p methylprednisolone; PC+AG, PC group treated with i.p Aminoguanidine; and PC+AG+MP, PC group treated with Aminoguanidine and methylprednisolone. Each group had seven animals. Blood and lung tissues were studied biochemically and histopathologically. When compared groups according to serum levels of biomarkers, serum YKL-40, nitrate-nitrite, catalase, and TBARS levels were significant different. Serum YKL-40 levels were decreased after treatments in three groups. The serum YKL-40 levels in PC+AG group were lower than the other treatment groups, especially compared to PC + MP (p=0.028). Serum nitrate-nitrite levels were decreased in all treatment groups (PC+MP, PC+AG and PC+MP+AG). The lowest levels were measured in PC+MP+AG; but there was no statistically significant difference compared to PC group (p>0.05). Serum catalase levels were increased in all treatment groups. The higher levels were measured in PC+MP+AG than the other single treatment groups; however, PC+MP+AG and PC+MP were statistically significant different compared to PC group (p=0.001 and p=0.002 respectively). Serum TBARS levels were decreased in all treatment groups compared to Sham group (p<0.001) and PC group (p<0.001). The lowest levels were measured in PC+MP+AG compared to PC group (p<0.001). Histopathologic and immunohistochemical staining scores were decreased at all the treatment groups, especially PC+MP+AG. We suggest the use of combined treatment of methylprednisolone and aminoguanidine for the treatment of pulmonary contusion.

Effects of maternal iodine deficiency and thyroidectomy on basal neuroendocrine function in rat pups

1997 ◽  
Vol 152 (3) ◽  
pp. 423-430 ◽  
Author(s):  
K Kondo ◽  
A Levy ◽  
S L Lightman
Keyword(s):  
Growth Hormone ◽  
Iodine Deficiency ◽  
Sprague Dawley ◽  
Transcript Levels ◽  
Releasing Hormone ◽  
Time Points ◽  
Neuroendocrine Function ◽  
Rat Pups ◽  
Sprague Dawley Rats ◽  
Time Point

We have used in situ hybridization histochemistry to investigate the effects of maternal thyroidectomy and chronic maternal iodine deficiency on basal neuroendocrine function in rat pups. Specifically, we have measured hypothalamic thyrotrophin-releasing hormone (TRH) and pituitary thyroid-stimulating hormone (TSH) expression together with circulating levels of tri-iodothyronine (T3) in rat pups delivered from and suckled by thyroidectomized or iodine-deficient dams. Because of the close interaction between the thyroid, adrenal and growth hormone axes, we have also examined hypothalamic corticotrophin-releasing hormone (CRH) and growth hormone-releasing hormone (GRH) transcripts at the same time points: birth, 1 month and 2 months of age. Three weeks after surgical thyroidectomy, adult female Sprague–Dawley rats proved unable to carry pups to term and lactate successfully. Pups delivered from thyroidectomized dams given a small replacement dose of T3 during pregnancy were significantly lighter than controls (84 ± 3%) and had markedly depressed plasma T3 levels (36 ±6% of control). Hypothalamic CRH and GRH transcript levels were significantly decreased in pups at birth (to 8±2·5% and 24 ± 8% of control respectively) but had returned to normal by 1 month after delivery. Pituitary TSH transcript levels and hypothalamic levels of TRH transcripts, however, were similar to those of controls. Only one of seven dams fed a low-iodine diet for 6 months produced live pups, and these were too few in number to produce significant data. Dams fed a lowiodine diet from 4 months before mating, however, did produce live pups and although they were not significantly lighter than control pups at birth, by 1 month after birth, they were significantly lighter (72 ± 3% of controls). Circulating T3 levels were not significantly different from control at any time point examined. Hypothalamic TRH levels were significantly elevated at birth (451 ± 138% of control), but this difference was not maintained at 1 or 2 months after birth despite the lactating dams being maintained on the low-iodine diet. Pituitary TSH levels showed an upward trend at all time points that reached significance at 1 month after birth (204 ± 19%; P<0·05). Hypothalamic CRH and GRH transcript levels were not different from controls at any time point. In summary, chronic iodine deficiency or thyroidectomy with low-level T3 replacement in Sprague–Dawley rats markedly impaired fertility and the ability to carry pups to term, and produced an unexpectedly modest up-regulation of the hypothalamo–pituitary–thyroid axis and down-regulation of the hypothalamo–pituitary–adrenal axis. Journal of Endocrinology (1997) 152, 423–430

scholarly journals The Severity of Ischemia Varies in Sprague-Dawley Rats from Different Vendors

ISRN Stroke ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Simona Nikolova ◽  
Ting-Yim Lee ◽  
Robert Bartha
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cerebral Perfusion ◽  
Lesion Size ◽  
Lesion Volume ◽  
Resonance Imaging ◽  
Sprague Dawley ◽  
Functional Deficits ◽  
Time Points ◽  
Sprague Dawley Rats ◽  
Stroke Lesion

The purpose of this study was to compare acute cerebral perfusion measured by computed tomography, stroke lesion volume measured by magnetic resonance imaging, and motor function in Sprague-Dawley rats supplied by Charles River (Charles River, Quebec, Canada) and Harlan (Harlan, Michigan, USA). During the acute stages of ischemia (<3 hours), Sprague-Dawley rats supplied by Harlan had a greater reduction in blood flow (67%) than rats supplied by Charles River (37%). MRI at days 1 and 6 after ischemia showed larger lesions in the Charles River animals compared to Harlan animals (P<0.05) at both time points. Lesion volume decreased in both Charles River and Harlan rats at day 6 compared to day 1 (P<0.05) and corresponded to lesion size on histology. The Harlan animals had significant functional deficits (P<0.05) one day after surgery in postural hang reflex, forelimb placement, and tactile fraction first tests, whereas rats supplied by Charles River had no significant functional impairment as a result of surgery. The current study provides evidence that differences in response to ischemia between rats of the same strain supplied by different vendors should be an important consideration when animals are selected for the study of cerebral ischemia.

scholarly journals Rehabilitation training improves nerve injuries by affecting Notch1 and SYN

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 387-395
Author(s):  
Mao Jing ◽  
Yang Yi ◽  
Zhang Jinniu ◽  
Kan Xiuli ◽  
Wu Jianxian
Keyword(s):  
Immunohistochemical Staining ◽  
Mrna Levels ◽  
Chronic Cerebral Ischemia ◽  
Sprague Dawley ◽  
Nerve Injuries ◽  
Rehabilitation Training ◽  
Training Groups ◽  
Time Points ◽  
Sprague Dawley Rats ◽  
Brain Tissues

AbstractObjectiveThe aim of this study was to investigate the effects of rehabilitation training on Notch1 and synaptophysin (SYN) levels in brain tissues of rats with chronic cerebral ischemia.MethodsEighty-one male Sprague-Dawley rats were divided into nine groups: three Sham groups, three Model groups, and three training groups. There were nine rats in each group. At different time points, the apoptosis cell rate was analyzed by the TUNEL assay, and the expression levels of Notch1 and SYN in brain tissues were analyzed by immunohistochemical staining and RT-qPCR assay.ResultsThe apoptosis cell rate of training groups was significantly higher on day 28 (P < 0.05). The protein and mRNA levels of both Noth1 and SYN in training groups were significantly higher on day 28 (P < 0.05).ConclusionRehabilitation training could improve nerve cell apoptosis by increasing the expression of both Notch1 and SYN.

Differentiation of the airways epithelium of fetal rat tracheal organ explants in serum-free culture: SEM observations

1983 ◽  
Vol 41 ◽  
pp. 478-479
Author(s):  
J.A. McAteer ◽  
T.J. Cavanagh
Keyword(s):  
Culture Medium ◽  
Bovine Insulin ◽  
Penicillin G ◽  
Sprague Dawley ◽  
Epithelial Surface ◽  
Serum Free ◽  
Time Points ◽  
Sprague Dawley Rats ◽  
Fetal Rat ◽  
Rat Trachea

This report describes SEM observations on the maturation of airways epithelial surface features in organ explants of fetal rat trachea. Tracheal explants were prepared from fetuses of timed pregnant Sprague-Dawley rats (16 days postcoitum). Tracheas were isolated intact, each was cut into two segments and the explants transferred to submersion culture (unsupported) in 3.5 ml culture medium within 60 mm Petri dishes (5% CO2 in air, humidified). Cultures were maintained in a component defined, serum-free, hormone supplemented medium patterned after medium K-l of Taub et al. Nutrient medium F12K was prepared with sodium bicarbonate (2.0 mg/ml), 10 mM HEPES, 10 nM Na2SeO3-5H2O, BSA (0.1%) and antibiotics (penicillin G, 100 U/ml; gentamicin sulfate, 10 ug/ml), pH 7.35. The medium was supplemented with five hormones including; bovine insulin, 5 ug/ml; human transferrin, 5 ug/ml; corticosterone 10-7M; PGE1, 25 ng/ml; and T3, 5xl0-12M. The medium was replaced every other day. Explants were processed for SEM by routine methods (2) at various time points throughout an 8 day culture period.

Frequency dependence of acoustic parameters of freshly excised tissues of Sprague Dawley rats

Ultrasonics ◽  
1977 ◽  
Vol 15 (4) ◽  
pp. 179-182 ◽  
Author(s):  
P. Bhagat ◽  
M. Kadaba ◽  
R. Ware ◽  
W. Cockerill
Keyword(s):  
Frequency Dependence ◽  
Sprague Dawley ◽  
Acoustic Parameters ◽  
Sprague Dawley Rats ◽  
Excised Tissues

scholarly journals EXTH-71. IND-ENABLING CHARACTERIZATION OF ONC206 AS THE NEXT BITOPIC DRD2 ANTAGONIST FOR NEURO-ONCOLOGY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi97-vi97 ◽  
Author(s):  
Varun Prabhu ◽  
Abed Rahman Kawakibi ◽  
Neel Madhukar ◽  
Mathew Garnett ◽  
Ultan McDermott ◽  
...  
Keyword(s):  
Body Weight ◽  
Cell Lines ◽  
Body Weight Gain ◽  
Human Fibroblasts ◽  
Xenograft Model ◽  
Therapeutic Window ◽  
Sprague Dawley ◽  
Toxic Dose ◽  
Biodistribution Studies ◽  
Sprague Dawley Rats

Abstract ONC201 is the first clinical bitopic antagonist of DRD2, an oncogenic receptor in brain and neuroendocrine tumors. ONC206, a derivative of ONC201 that shares the imipridone core structure, is also a bitopic DRD2 antagonist that exhibits enhanced non-competitive effects, high specificity, nanomolar potency, and disruption of DRD2 homodimers. Broad nanomolar efficacy of ONC206 (GI50 < 78-889nM, CellTitre-Glo, 72h) was observed in >1,000 GDSC cancer cell lines. Maximal ONC206 sensitivity was observed in pheochromocytoma, high-grade gliomas, neuroblastoma, medulloblastoma, sarcoma and cholangiocarcinoma cell lines exhibiting a DRD2+/DRD5- RNA expression signature. An exposure time of 48h at nanomolar concentrations was sufficient for maximal inhibition of tumor cell viability. ONC206 reduced the viability of normal human fibroblasts at higher doses (GI50 > 5µM), suggesting a wide therapeutic window. Antitumor efficacy without body weight loss was observed with 50 mg/kg weekly oral ONC206 in a dopamine-secreting HuCCT1 cholangiocarcinoma subcutaneous xenograft model. Biodistribution studies in Sprague-Dawley rats revealed a ~12 µM plasma Cmax with a systemic terminal half-life of ~6 hours upon a single oral dose of 50 mg/kg. Additionally, 5–10 fold higher ONC206 concentrations were observed in adrenal gland, bile duct, brain and bone marrow relative to plasma. Nanomolar concentrations were also observed in the CSF above DRD2 antagonism thresholds, unlike ONC201. GLP toxicology studies with weekly oral ONC206 in Sprague-Dawley rats and beagle dogs revealed no dose-limiting toxicities. Mild and reversible decreased body weight and/or body weight gain with no effects on food consumption were observed at the highest evaluated dose in both species. The highest non-severely toxic dose (HNSTD) was ≥ 16.7 mg/kg in dogs and ≥ 50 mg/kg in rats that exceeds efficacious doses in preclinical models. Using standard allometric scaling, a 90 mg starting dose of ONC206 was selected for the first-in-human clinical trial in biomarker-defined adult recurrent CNS tumors.

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