rat plasma
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2022 ◽  
Vol 13 ◽  
Author(s):  
Ning Cao ◽  
Shuping Li ◽  
Aimin Xu ◽  
Manlin Li ◽  
Xiaoguang Zou ◽  
...  

ObjectiveSeveral β-carboline alkaloids (βCBs), such as harmine, harmaline, harmane, and nor-harmane, are effective for Alzheimer’s disease mouse models. They can be found in some plants, common foodstuffs, and blank plasma of various mammals. However, whether these compounds in mammals are exogenous or endogenous remain unclear.MethodsThe exposure levels of βCBs and of neurotransmitters in plasma and tissues of pup rats, aging rats, mice of different physiological states, and healthy volunteers were detected by using UPLC-MS/MS. Plasma and tissue samples from 110 newborn rats up to 29 days old at 11 sampling points were collected and were analyzed to determine the concentration variation of βCBs in the developmental phase of newborn rats. The plasma of rats aged 2 to 18 months was used to detect the variation trend of βCBs and with some neurotransmitters. The plasma samples of normal C57BL/6 mice, APP/PS1 double transgenic mice, and scopolamine-induced memory impairment mice were collected and were analyzed to compare the difference of βCBs in different physiological states. The exposure levels of βCBs such as harmine, harmaline, and harmane in plasma of 550 healthy volunteers were also detected and analyzed on the basis of gender, race, and age.ResultsResults showed that harmine was the main compound found in rats, mice, and human, which can be detected in a newborn rat plasma (0.16 ± 0.03 ng/ml) and brain (0.33 ± 0.14 ng/g) without any exogenous consumption. The concentration of harmine in rat plasma showed a decreasing trend similar to the exposure levels of neurotransmitters such as 5-hydroxytryptamine, acetylcholine chloride, glutamic acid, tyrosine, and phenylalanine during the growth period of 18 months. The harmine exposure in rats and human indicates high dependence on the physiological and pathological status such as aging, gender, and race.ConclusionThe dynamic changes of harmine exposure in different animals and human, in vivo, at developmental and physiological states indicate that harmine is a naturally and widely distributed endogenous substance in different mammals and human. In addition to exogenous ingestion, spontaneous synthesis might be another important source of harmine in mammals, which should be verified by further experiment.


2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Yongpeng Xie ◽  
Hui Zheng ◽  
Zhifang Mou ◽  
Yanli Wang ◽  
Xiaomin Li

Background. The energy delivered by a ventilator to the respiratory system in one minute is defined as mechanical power (MP). However, the effect of ventilator-induced lung injury (VILI) in patients suffering from acute respiratory distress syndrome (ARDS) is still unknown. Our previous studies revealed that CXCL10 may be a potential biomarker of lung injury in ARDS. Therefore, the aim of this study was to compare the lung injury of rats and patients under different MP conditions to explore the involvement of CXCL10 and its receptor CXCR3 in VILI. Methods. Patients were divided into the high mechanical power group (HMPp group) and low mechanical power group (LMPp group), while rats were assigned to the high mechanical power group (HMPr group), medium mechanical power group (MMPr group), and low mechanical power group (LMPr group). CXCL10 and CXCR3 plasma content in ARDS patients and rats under ventilation at different MP was measured, as well as their protein and mRNA expression in rat lungs. Results. CXCL10 and CXCR3 content in the plasma of ARDS patients in the HMPp was significantly higher than that in the LMPp. The increase of MP during mechanical ventilation in the rats gradually increased lung damage, and CXCL10 and CXCR3 levels in rat plasma gradually increased with the increase of MP. CXCL10 and CXCR3 protein and mRNA expression in the HMPr group and MMPr group was significantly higher than that in the LMPr group ( P < 0.05 ). More mast cells were present in the trachea, bronchus, blood vessels, and lymphatic system in the rat lungs of the HMPr group, and the number of mast cells in the HMPr group ( 13.32 ± 3.27 ) was significantly higher than that in the LMPr group ( 3.25 ± 0.29 ) ( P < 0.05 ). Conclusion. The higher the MP, the more severe the lung injury, and the higher the CXCL10/CXCR3 expression. Therefore, CXCL10/CXCR3 might participate in VILI by mediating mast cell chemotaxis.


Author(s):  
RAMYA SRI SURA ◽  
SUBRAHMANYAM CVS ◽  
SHYAM SUNDER RACHAMALLA

Objective: A novel, simple, precise, accurate, sensitive, and reproducible HPLC method for determining clopidogrel bisulfate in Wistar rat plasma was developed and validated. Methods: The chromatographic separation was performed using Xterra C18 (250 x 4.6 mm, 5μ) column. Mobile phase composed of Acetonitrile ACN: 0.05M potassium dihydrogen orthophosphate buffer pH 4.2 and in the ratio of 75:25% v/v at a flow rate of 1.2 ml/min. Detection was carried out using a PDA detector at 220 nm. The bioanalytical clopidogrel method was validated as per ICH guidelines. Results: The selected chromatographic condition was found to efficiently separate clopidogrel bisulfate (RT-2.838 min). The calibration curve was linear over the concentration range 40-200 ng/ml in Wistar rat plasma with a correlation coefficient of 0.999, respectively. The precision study revealed that the cumulative percentage variation was within the acceptable limit, and accuracy research showed the value of mean percent recovery between 99.72-99.83 %. Conclusion: A simple, rapid, specific, accurate, and precise analytical method was developed and validated using Wistar rat plasma. The technique was strictly validated according to the ICH guidelines. Acquired results demonstrate that the proposed strategy can be effortlessly and advantageously applied for routine analysis of clopidogrel in the Wistar rat plasma.


2022 ◽  
Author(s):  
Kusuma Kumari Garikapati ◽  
Ammu V. V. V. Ravi Kiran ◽  
Praveen Thaggikuppe Krishnamurthy ◽  
Narenderan S. T ◽  
Babu. B ◽  
...  

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 339
Author(s):  
Guru R. Valicherla ◽  
Roshan A. Katekar ◽  
Shailesh Dadge ◽  
Mohammed Riyazuddin ◽  
Anees A. Syed ◽  
...  

PSTi8 is a pancreastatin inhibitory peptide that is effective in the treatment of diabetic models. This study investigates the pharmacokinetic (PK) properties of PSTi8 in Sprague Dawley rats, for the first time. In vitro and in vivo PK studies were performed to evaluate the solubility, stability in plasma and liver microsomes, plasma protein binding, blood–plasma partitioning, bioavailability, dose proportionality, and gender difference in PK. Samples were analyzed using the validated LC-MS/MS method. The solubility of PSTi8 was found to be 9.30 and 25.75 mg/mL in simulated gastric and intestinal fluids, respectively. The protein binding of PSTi8 was estimated as >69% in rat plasma. PSTi8 showed high stability in rat plasma and liver microsomes and the blood–plasma partitioning was >2. The bioavailability of PSTi8 after intraperitoneal and subcutaneous administration was found to be 95.00 ± 12.15 and 78.47 ± 17.72%, respectively, in rats. PSTi8 showed non-linear PK in dose proportionality studies, and has no gender difference in the PK behavior in rats. The high bioavailability of PSTi8 can be due to high water solubility and plasma protein binding, low clearance and volume of distribution. Our in vitro and in vivo findings support the development of PSTi8 as an antidiabetic agent.


2022 ◽  
Author(s):  
Seiya Tanaka ◽  
Aphichat Trakooncharoenvit ◽  
Miyu Nishikawa ◽  
Shin-ichi Ikushiro ◽  
Hiroshi Hara
Keyword(s):  

Quercetin and methylquercetin are present as a variety of sulfate and glucuronide conjugates in the plasma of quercetin-fed rats and humans. Quercetin conjugates have various physiological activities, depending on the...


2021 ◽  
Vol 15 (1) ◽  
pp. 52
Author(s):  
Xiuqing Gao ◽  
Robert Y. L. Tsai ◽  
Jing Ma ◽  
Yang Wang ◽  
Xiaohua Liu ◽  
...  

Oxaliplatin (OXP), a third-generation platinum-based chemotherapy drug, was often indirectly analyzed via total platinum by an ICP-MS because it was difficult to directly quantify using an LC-MS/MS method, due to its instability, bad column separability and severe MS signal inhibition. Here, we developed and validated a specific, sensitive and reproducible LC-MS/MS method for the quantification of OXP itself in rat plasma and tongue tissue on a SCIEX 4000 QTRAP® MS/MS system equipped with a Phenomenex Lux 5u Cellulose-1 column (250 × 4.6 mm, 5 μm). This method was validated at the lower limit of detection (LOD) and the lower limit of quantitation (LLOQ) of 5 ng/mL and 10 ng/mL, with linearity of 10–5000 ng/mL (r2 > 0.99) and 10–2500 ng/mL (r2 > 0.99), in rat plasma and tongue homogenates, respectively. The intra- and inter-day precision (CV%) and accuracy (RE%) were within 15% for LLOQ, low-, medium- and high-quality control samples. The mean extraction recoveries were around 50% and 80% for plasma and tongue homogenates, respectively. This assay was successfully applied to pharmacokinetics study following intravenous administration of OXP, as well as tongue tissue distribution after 1 h and 4 h of a novel oral mucosal patch application.


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