A comparative study on pharmacokinetics and tissue distribution of 5-hydroxy-4-methoxycanthin-6-one and its metabolite in normal and dextran sodium sulfate-induced colitis rats by HPLC-MS/MS

2020 ◽  
Author(s):  
Fangle Liu ◽  
Qiuyu Zhang ◽  
Chaozhan Lin ◽  
Yufeng Yao ◽  
Meiqi Wang ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Sodium Sulfate ◽  
Intestinal Tract ◽  
Dextran Sodium Sulfate ◽  
Main Metabolite ◽  
Pathological Conditions ◽  
Significant Difference ◽  
Distribution Studies ◽  
Existing Form

Abstract Objectives This study aimed to investigate the existing form of 5-hydroxy-4-methoxycanthin-6-one (PQ-A) in vivo after oral administration and the effects on its pharmacokinetics and tissue distribution by colitis. Methods A rapid HPLC-MS/MS method was established to simultaneously determine PQ-A and its main metabolite, 1-methoxicabony-β-carboline (PQ-B), in biological samples acquired from normal and dextran sodium sulfate (DSS)-induced colitic rats administered orally with PQ-A. Then, the pharmacokinetics of both PQ-A and PQ-B, and tissue distribution of PQ-A in the above two states were analysed. Key findings The pharmacokinetic results showed that the prototype of PQ-A was the main existing form in both physiological and pathological conditions. And significant difference between the above two status in pharmacokinetics of PQ-A was observed, such as higher exposure and longer elimination in colitis than that in normal rats. It suggested that the pharmacokinetics of medications for colitis was affected by enteritis. The tissue distribution studies displayed that PQ-A mainly accumulated in intestinal tract. Especially, the distribution of PQ-A in intestinal tract was increased obviously in colitic rats. Conclusions These results contributed to further illuminate the ADME process of PQ-A in different status and were prospected to be the reference to the clinical application of similar medicines in pathological states.

scholarly journals Tetrasaccharide iteration synthesis of a heparin-like dodecasaccharide and radiolabelling for in vivo tissue distribution studies

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Steen U. Hansen ◽  
Gavin J. Miller ◽  
Claire Cole ◽  
Graham Rushton ◽  
Egle Avizienyte ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Distribution Studies

scholarly journals Dried Leaf Artemisia Annua Improves Bioavailability of Artemisinin via Cytochrome P450 Inhibition and Enhances Artemisinin Efficacy Downstream

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 254 ◽  
Author(s):  
Matthew R. Desrosiers ◽  
Alexis Mittleman ◽  
Pamela J. Weathers
Keyword(s):  
Tissue Distribution ◽  
Artemisia Annua ◽  
Liver Microsomes ◽  
Hepatic Metabolism ◽  
Oral Consumption ◽  
Tnf Α ◽  
Ic50 Values ◽  
Distribution Studies ◽  
Pass Metabolism

Artemisia annua L. and artemisinin, have been used for millennia to treat malaria. We used human liver microsomes (HLM) and rats to compare hepatic metabolism, tissue distribution, and inflammation attenuation by dried leaves of A. annua (DLA) and pure artemisinin. For HLM assays, extracts, teas, and phytochemicals from DLA were tested and IC50 values for CYP2B6 and CYP3A4 were measured. For tissue distribution studies, artemisinin or DLA was orally delivered to rats, tissues harvested at 1 h, and blood, urine and feces over 8 h; all were analyzed for artemisinin and deoxyartemisinin by GC-MS. For inflammation, rats received an intraperitoneal injection of water or lipopolysaccharide (LPS) and 70 mg/kg oral artemisinin as pure drug or DLA. Serum was collected over 8 h and analyzed by ELISA for TNF-α, IL-6, and IL-10. DLA-delivered artemisinin distributed to tissues in higher concentrations in vivo, but elimination remained mostly unchanged. This seemed to be due to inhibition of first-pass metabolism by DLA phytochemicals, as demonstrated by HLM assays of DLA extracts, teas and phytochemicals. DLA was more effective than artemisinin in males at attenuating proinflammatory cytokine production; the data were less conclusive in females. These results suggest that the oral consumption of artemisinin as DLA enhances the bioavailability and anti-inflammatory potency of artemisinin.

Malt1 blocks IL-1β production by macrophages in vitro and limits dextran sodium sulfate-induced intestinal inflammation in vivo

2018 ◽  
Vol 104 (3) ◽  
pp. 557-572 ◽  
Author(s):  
Mahdis Monajemi ◽  
Yvonne C. F. Pang ◽  
Saelin Bjornson ◽  
Susan C. Menzies ◽  
Nico van Rooijen ◽  
...  
Keyword(s):  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Dextran Sodium Sulfate

scholarly journals HPLC-MS/MS-Mediated Analysis of the Pharmacokinetics, Bioavailability, and Tissue Distribution of Schisandrol B in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-12 ◽  
Author(s):  
Dahu Liang ◽  
Zijing Wu ◽  
Yanhao Liu ◽  
Chao Li ◽  
Xianghong Li ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Oral Bioavailability ◽  
Internal Standard ◽  
Rat Plasma ◽  
Absolute Bioavailability ◽  
Sprague Dawley ◽  
Linear Calibration ◽  
Tissue Homogenates ◽  
Distribution Studies

Schisandrol B, a lignan isolated from dried Schisandra chinensis fruits, has been shown to exhibit hepatoprotective, cardioprotective, renoprotective, and memory-enhancing properties. This study sought to design a sensitive and efficient HPLC-MS/MS approach to measuring Schisandrol B levels in rat plasma and tissues in order to assess the pharmacokinetics, oral bioavailability, and tissue distributions of this compound in vivo. For this analysis, bifendate was chosen as an internal standard (IS). A liquid-liquid extraction (LLE) approach was employed for the preparation of samples that were subsequently separated with an Agilent ZORBAX Eclipse XDB-C18 (4.6 × 150 mm, 5 μm) column with an isocratic mobile phase consisting of methanol and water containing 5 mM ammonium acetate and 0.1% formic acid (90 : 10, v/v). A linear calibration curve was obtained over the 5–2000 ng/mL and 1–1000 ng/mL ranges for plasma samples and tissue homogenates, respectively. This established method was then successfully applied to investigate the pharmacokinetics, oral bioavailability, and tissue distributions of Schisandrol B in Sprague-Dawley (SD) rats that were intravenously administered 2 mg/kg of Schisandrol B monomer, intragastrically administered Schisandrol B monomer (10 mg/kg), or intragastrically administered 6 mL/kg SCE (equivalent to 15 mg/kg Schisandrol B monomer). The oral absolute bioavailability of Schisandrol B following intragastric Schisandrol B monomer and SCE administration was approximately 18.73% and 68.12%, respectively. Tissue distribution studies revealed that Schisandrol B was distributed throughout several tested tissues, with particular accumulation in the liver and kidneys. Our data represent a valuable foundation for future studies of the pharmacologic and biological characteristics of Schisandrol B.

scholarly journals The synthesis of [14C]streptozotocin and its distribution and excretion in the rat

1974 ◽  
Vol 142 (3) ◽  
pp. 673-683 ◽  
Author(s):  
Eric H. Karunanayake ◽  
David J. Hearse ◽  
Graham Mellows
Keyword(s):  
Biological Activity ◽  
Tissue Distribution ◽  
Renal Clearance ◽  
Dose Response ◽  
Whole Body ◽  
Response Curves ◽  
Intestinal Excretion ◽  
Metabolic Transformation ◽  
Distribution Studies

[14C]Streptozotocin was synthesized specifically labelled at three positions in the molecule. The biological activity of synthetic streptozotocin was characterised by studies in vivo of its diabetogenic activity and its dose–response curves. After this characterization the excretion pattern of all three labelled forms of streptozotocin was studied. With [1-14C]streptozotocin and [2′-14C]streptozotocin the injected radioactivity was excreted (approx. 70% and 80% respectively) mainly in the urine, the greater part of the excretion occurring in the first 6h period; small amounts (approx. 9% and 8% respectively) were found in the faeces. In contrast, with [3′-methyl-14C]streptozotocin a much smaller proportion (approx. 42%) of the injected radioactivity was excreted in the urine, the major proportion appearing in the first 6h, whereas approx. 53% of the injected radioactivity was retained in the carcasses. In whole-body radioautographic studies very rapid renal clearance and hepatic accumulation of the injected radioactivity was observed with all three labelled forms of the drug. There was some evidence for biliary and intestinal excretion. Major differences were apparent in the tissue-distribution studies, with each of the three labelled forms, particularly with [3′-methyl-14C]streptozotocin. There was no accumulation of [1-14C]streptozotocin in the pancreas for the 6h period after administration. However, with [3′-methyl-14C]streptozotocin (and also [2′-14C]streptozotocin) there was evidence of some pancreatic accumulation after 2h. The results indicate that streptozotocin is subjected to considerable metabolic transformation and to rapid renal clearance. The implication of these suggestions is evaluated with particular reference to the diabetogenic action of streptozotocin.

scholarly journals Anti-Inflammatory Effects ofInonotus obliquusin Colitis Induced by Dextran Sodium Sulfate

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Se Young Choi ◽  
Sun Jin Hur ◽  
Chi Sun An ◽  
Yun Hui Jeon ◽  
Young Jun Jeoung ◽  
...  
Keyword(s):  
Sodium Sulfate ◽  
Dextran Sodium Sulfate ◽  
Raw264.7 Cells ◽  
Average Weight ◽  
Inonotus Obliquus ◽  
Signal Transducers ◽  
Commercial Diet ◽  
Treatment Groups ◽  
Significant Difference ◽  
Group B

A total of 28 male BALB/c mice (average weight 20.7 ± 1.6 g) were divided into 4 treatment groups and fed a commercial diet (A), a commercial diet + induced colitis by dextran sodium sulfate (DSS) (B),Inonotus obliquus(IO) administration (C), and IO administration + induced colitis by DSS (D). IO treatment (C, D) decreased the expression of tumor necrosis factor (TNF)-αand signal transducers and activators of transcription (STAT)1 compared to those of the colitis induced group (B). The expressions of IL-4 and STAT6 were decreased in group D compared to the colitis induced group (B). The serum immunoglobulin (Ig)E level decreased in IO treatment groups (C, D) compared to no IO treatment groups (A and B) although there was no significant difference between the IO treatment groups. Extract from IO itself had a weak cytotoxic effect on murine macrophage cell line (RAW264.7 cells). Extract from IO inhibited lipopolysaccharide- (LPS-) induced, TNF-α, STAT1, pSTAT1, STAT6, and pSTAT6 production in RAW264.7 cells.

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