scholarly journals The Pharmacokinetics of Medetomidine Administered Subcutaneously during Isoflurane Anaesthesia in Sprague-Dawley Rats

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1050 ◽  
Author(s):  
Leila T. Kint ◽  
Bhedita J. Seewoo ◽  
Timothy H. Hyndman ◽  
Michael W. Clarke ◽  
Scott H. Edwards ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Anaesthetic Agent ◽  
Sprague Dawley ◽  
Isoflurane Anaesthesia ◽  
Future Studies ◽  
Rodent Brain ◽  
Sprague Dawley Rats ◽  
Combined Use ◽  
Steady State Serum ◽  
Brain Fmri

Anaesthetic protocols involving the combined use of a sedative agent, medetomidine, and an anaesthetic agent, isoflurane, are increasingly being used in functional magnetic resonance imaging (fMRI) studies of the rodent brain. Despite the popularity of this combination, a standardised protocol for the combined use of medetomidine and isoflurane has not been established, resulting in inconsistencies in the reported use of these drugs. This study investigated the pharmacokinetic detail required to standardise the use of medetomidine and isoflurane in rat brain fMRI studies. Using mass spectrometry, serum concentrations of medetomidine were determined in Sprague-Dawley rats during medetomidine and isoflurane anaesthesia. The serum concentration of medetomidine for administration with 0.5% (vapouriser setting) isoflurane was found to be 14.4 ng/mL (±3.0 ng/mL). The data suggests that a steady state serum concentration of medetomidine when administered with 0.5% (vapouriser setting) isoflurane can be achieved with an initial subcutaneous (SC) dose of 0.12 mg/kg of medetomidine followed by a 0.08 mg/kg/h SC infusion of medetomidine. Consideration of these results for future studies will facilitate standardisation of medetomidine and isoflurane anaesthetic protocols during fMRI data acquisition.

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.

Subchronic Toxicity of S-111-S-WB in Sprague Dawley Rats

2010 ◽  
Vol 29 (4) ◽  
pp. 358-371 ◽  
Author(s):  
Jozef J. W. M. Mertens ◽  
Daniel W. Sved ◽  
Gary B. Marit ◽  
Nichole R. Myers ◽  
Phil L. Stetson ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Steady State ◽  
Ammonium Salts ◽  
Serum Concentrations ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Lower Serum ◽  
Sprague Dawley Rats ◽  
Steady State Serum ◽  
Effect Level

S-111-S-WB, a mixture of perfluoro fatty acid ammonium salts (C6-C13), was administered orally to Crl:CD (SD)IGS-BR rats. Higher hepatic β-oxidation and liver weights with hepatocellular hypertrophy were present at the 0.125 and 0.6 mg/kg/d dosage. The 0.6 mg/kg/d males developed hepatocellular degeneration and necrosis. Lower serum protein and higher bilirubin and BUN were seen in the 0.6 mg/kg/d males and lower globulin and higher alkaline phosphatase in the 0.125 mg/kg/d males and 0.6 mg/kg/d animals. After 2 weeks, serum concentrations of pentadecafluorooctanoic acid (C8), heptadecafluorononanoic acid (C9), perfluoroundecanoic acid (C11), and perfluorotridecanoic acid (C13) were constant for at least 8 hours. After 90 days, only C9 in the 0.025 mg/kg/d females had reached steady state. Serum C8 and C9 concentrations in the males were 10-fold higher than in the females, whereas C11 and C13 were similar for both genders. The main elimination was via the urine for C8 (males) and C9 (females), and via the feces for C11 and C13. The no-observed-effect level (NOEL) was 0.025 mg/kg/d for the males and 0.125 mg/kg/d for the females.

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.

scholarly journals Linezolid Inhibited Synthesis of ATP in Mitochondria: Based on GC-MS Metabolomics and HPLC Method

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Xuemei Ye ◽  
Aifang Huang ◽  
Xianqin Wang ◽  
Congcong Wen ◽  
Lufeng Hu ◽  
...  
Keyword(s):  
Serum Concentration ◽  
High Performance ◽  
Multidrug Resistant ◽  
Hplc Method ◽  
Control Group ◽  
Sprague Dawley ◽  
High Group ◽  
Atp Concentration ◽  
Sprague Dawley Rats ◽  
Serious Infections

Linezolid has been widely used in serious infections for its effective inhibiting effect against multidrug-resistant gram-positive pathogens. However, linezolid caused severe adverse reactions, such as thrombocytopenia, anaemia, optic neuropathy, and near-fatal serotonin syndrome. In order to investigate the toxicity of linezolid, twenty-four Sprague-Dawley rats were randomly divided into: control group (n=7), low-group (n=8), and high-group (n=9). The rats of low-group and high-group were given by gavage with linezolid 60 and 120 mg/kg/day for 7 days, respectively. The serum concentration of linezolid was determined by high performance liquid chromatography (HPLC); blood metabolic change was analyzed by gas chromatography-mass spectrometer (GC-MS). Adenosine triphosphate (ATP) concentration in HepG2-C3A after being cultured with linezolid was determined by HPLC. The results showed that there were six metabolites and nine metabolites had statistical differences in low-group and high-group (P<0.05). The trimethyl phosphate was the most significant indicator in those changed metabolites. Except for d-glucose which was slightly increased in low-group, octadecanoic acid, cholest-5-ene, hexadecanoic acid, α-linolenic acid, eicosapentaenoic acid, 9,12-Octadecadienoic acid, and docosahexaenoic acid were all decreased in low-group and high-group. ATP concentration was decreased in HepG2-C3A after cultured with linezolid. In conclusion, the toxicity of linezolid is related to its serum concentration. Linezolid may inhibit the synthesis of ATP and fatty acid.

Toxicological effects of carbosulfan in rats

2015 ◽  
Vol 32 (7) ◽  
pp. 1335-1343 ◽  
Author(s):  
Christopher Didigwu Nwani ◽  
Narottam Das Agrawal ◽  
Suchita Raghuvanshi ◽  
Amita Jaswal ◽  
Sadhana Shrivastava ◽  
...  
Keyword(s):  
Antioxidant Defense ◽  
Reduced Glutathione ◽  
Sprague Dawley ◽  
Future Studies ◽  
Toxicological Effects ◽  
Stress Markers ◽  
Sprague Dawley Rats ◽  
Study Results ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
The Impact

Carbosulfan is often used in agriculture for pest control on crops and for treatment against pyrethroid-resistant mosquitoes. This study investigated the impact of carbosulfan on oxidative stress markers, antioxidant defense, hematological, biochemical, and enzymological parameters in Sprague Dawley rats. Rats were orally administered carbosulfan doses of 1.02 to 10.20 mg/kg body weight daily; after 96 h, blood samples were taken, and the liver, kidney, and brain were dissected out for study. Results indicate that carbosulfan significantly increased the levels of lipid peroxidation and suppressed the activity of reduced glutathione, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase, and adenosine triphosphatase. A mixed trend was observed in the activity of superoxide dismutase, while an increase was observed in the levels of serum uric acid, urea, aspartate aminotransferase, and alanine aminotransferase. Hemoglobin and albumin levels decreased but no significant differences were observed in creatinine and bilirubin levels. Future studies should include a more detailed analysis of the effects of chronic carbosulfan exposure on these biomarkers to further assess the impact of the pesticide on mammalian models.

Ultrasound-assisted convection-enhanced delivery to the brain in vivo with a novel transducer cannula assembly

2012 ◽  
Vol 117 (6) ◽  
pp. 1128-1140 ◽  
Author(s):  
George K. Lewis ◽  
Zachary R. Schulz ◽  
Susan C. Pannullo ◽  
Teresa L. Southard ◽  
William L. Olbricht
Keyword(s):  
Continuous Wave ◽  
Sprague Dawley ◽  
Convection Enhanced Delivery ◽  
Rodent Brain ◽  
Sprague Dawley Rats ◽  
Ultrasound Assisted ◽  
Group 2 ◽  
The Brain ◽  
Group 1

Object In convection-enhanced delivery (CED), drugs are infused locally into tissue through a cannula inserted into the brain parenchyma to enhance drug penetration over diffusion strategies. The purpose of this study was to demonstrate the feasibility of ultrasound-assisted CED (UCED) in the rodent brain in vivo using a novel, low-profile transducer cannula assembly (TCA) and portable, pocket-sized ultrasound system. Methods Forty Sprague-Dawley rats (350–450 g) were divided into 2 equal groups (Groups 1 and 2). Each group was divided again into 4 subgroups (n = 5 in each). The caudate of each rodent brain was infused with 0.25 wt% Evans blue dye (EBD) in phosphate-buffered saline at 2 different infusion rates of 0.25 μl/minute (Group 1), and 0.5 μl/minute (Group 2). The infusion rates were increased slowly over 10 minutes from 0.05 to 0.25 μl/minute (Group 1) and from 0.1 to 0.5 μl/minute (Group 2). The final flow rate was maintained for 20 minutes. Rodents in the 4 control subgroups were infused using the TCA without ultrasound and without and with microbubbles added to the infusate (CED and CED + MB, respectively). Rodents in the 4 UCED subgroups were infused without and with microbubbles added to the infusate (UCED and UCED + MB) using the TCA with continuous-wave 1.34-MHz low-intensity ultrasound at a total acoustic power of 0.11 ± 0.005 W and peak spatial intensity at the cannula tip of 49.7 mW/cm2. An additional 4 Sprague-Dawley rats (350–450 g) received UCED at 4 different and higher ultrasound intensities at the cannula tip ranging from 62.0 to 155.0 mW/cm2 for 30 minutes. The 3D infusion distribution was reconstructed using MATLAB analysis. Tissue damage and morphological changes to the brain were assessed using H & E. Results The application of ultrasound during infusion (UCED and UCED + MB) improved the volumetric distribution of EBD in the brain by a factor of 2.24 to 3.25 when there were no microbubbles in the infusate and by a factor of 1.16 to 1.70 when microbubbles were added to the infusate (p < 0.001). On gross and histological examination, no damage to the brain tissue was found for any acoustic exposure applied to the brain. Conclusions The TCA and ultrasound device show promise to improve the distribution of infused compounds during CED. The results suggest further studies are required to optimize infusion and acoustic parameters for small compounds and for larger molecular weight compounds that are representative of promising antitumor agents. In addition, safe levels of ultrasound exposure in chronic experiments must be determined for practical clinical evaluation of UCED. Extension of these experiments to larger animal models is warranted to demonstrate efficacy of this technique.

scholarly journals Bursting by taste-responsive cells in the rodent brain stem

2015 ◽  
Vol 113 (7) ◽  
pp. 2434-2446
Author(s):  
John-Paul Baird ◽  
Michael G. Tordoff ◽  
Stuart A. McCaughey
Keyword(s):  
Brain Stem ◽  
Significant Positive Correlation ◽  
Short Interval ◽  
Neural Systems ◽  
Solitary Tract ◽  
Sprague Dawley ◽  
Short Intervals ◽  
Rodent Brain ◽  
Sprague Dawley Rats ◽  
Gustatory Neurons

Neurons that fire in bursts have been well-characterized in vision and other neural systems, but not in taste systems. We therefore examined whether brain stem gustatory neurons fire in bursts during spontaneous activity and, if so, whether such cells differ from nonbursting cells in other characteristics. We looked at neurons in the nucleus of the solitary tract (NST) of C57BL/6ByJ (B6) and 129P3/J (129) mice, and in the NST and parabrachial nucleus (PBN) of Sprague-Dawley rats. Many NST cells fired frequently with short intervals characteristic of bursting, and such neurons differed from others in their responsiveness to taste compounds. In B6 mice and rats, there was a significant positive correlation between the prevalence of short-interval firing and the net spikes evoked by application of NaCl. In contrast, in 129 mice the prevalence of short intervals was positively correlated with the size of sucrose responses. We also compared breadth-of-tuning measures based on counting either all spikes or only those following short intervals, and we found narrower tuning for the latter in the NST of B6 mice and rats. There was little evidence of spontaneous bursting in the rat PBN, and firing patterns in this nucleus were not related to the size of taste-evoked responses. We suggest that bursting may be a strategy employed by the NST to amplify the postsynaptic impact of particular taste stimuli, depending on an animal's needs. Another function may be to sharpen breadth-of-tuning and thus enhance the contrast between stimuli of different taste qualities.

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