In Vitro Metabolism of Humantenine in Liver Microsomes from Human, Pig, Goat and Rat

2021 ◽  
Vol 22 ◽  
Author(s):  
Si-Juan Huang ◽  
Meng-Ting Zuo ◽  
Xue-Jia Qi ◽  
Xiao Ma ◽  
Zi-Yuan Wang ◽  
...  
Keyword(s):  
High Performance ◽  
Species Differences ◽  
Liver Microsomes ◽  
In Vitro Metabolism ◽  
Rat Liver Microsomes ◽  
Active Components ◽  
Toxicological Effects ◽  
Flight Mass Spectrometry ◽  
Toxic Plant

Background: Gelsemium elegans Benth（G. elegans） is a well-known toxic plant. Alkaloids are main active components of G. elegans. Currently, the metabolism of several alkaloids, such as gelsenicine, koumine, and gelsemine, has been widely studied. However, as one of the most important alkaloids in G. elegans, the metabolism of humantenine has not been studied yet. Methods: In order to elaborate on the in vitro metabolism of humantenine, a comparative analysis of its metabolic profile in human, pig, goat and rat liver microsomes was carried out using high-performance chromatography/quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS) for the first time. Results: Totally, ten metabolites of humantenine were identified in liver microsomes from human (HLMs), pig (PLMs), goat (GLMs) and rat (RLMs) based on the accurate MS/MS spectra. Five metabolic pathways of humantenine, including demethylation, dehydrogenation, oxidation, dehydrogenation and oxidation, and demethylation and oxidation, were proposed in this study. There were qualitative and quantitative species differences in the metabolism of humantenine among the four species. Conclusions: The in vitro metabolism of humantenine in HLMs, PLMs, GLMs and RLMs was studied by a sensitive and specific detection method based on HPLC/QqTOF-MS. The results indicated that there were species-related differences in the metabolism of humantenine. This work might be of great significance for the further research and explanation of species differences in terms of toxicological effects of G. elegans.

scholarly journals A Complete Study of Farrerol Metabolites Produced in Vivo and in Vitro

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3470
Author(s):  
Yin ◽  
Ma ◽  
Liang ◽  
Wang ◽  
Sun ◽  
...  
Keyword(s):  
High Performance ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Flight Mass Spectrometry ◽  
Multiple Data ◽  
Glucuronide Conjugation ◽  
Complete Study ◽  
Glucose Conjugation

Although farrerol, a characteristically bioactive constituent of Rhododendron dauricum L., exhibits extensive biological and pharmacological activities (e.g., anti-oxidant, anti-immunogenic, and anti-angiogenic) as well as a high drug development potential, its metabolism remains underexplored. Herein, we employed ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with multiple data post-processing techniques to rapidly identify farrerol metabolites produced in vivo (in rat blood, bile, urine and feces) and in vitro (in rat liver microsomes). As a result, 42 in vivo metabolites and 15 in vitro metabolites were detected, and farrerol shown to mainly undergo oxidation, reduction, (de)methylation, glucose conjugation, glucuronide conjugation, sulfate conjugation, N-acetylation and N-acetylcysteine conjugation. Thus, this work elaborates the metabolic pathways of farrerol and reveals the potential pharmacodynamics forms of farrerol.

In vitro metabolism in Sprague–Dawley rat liver microsomes of forsythoside A in different compositions of Shuang–Huang–Lian

Fitoterapia ◽  
2011 ◽  
Vol 82 (8) ◽  
pp. 1222-1230 ◽  
Author(s):  
Wei Zhou ◽  
Liu-qing Di ◽  
Jin-jun Shan ◽  
Xiao-lin Bi ◽  
Le-tian Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Metabolism ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Sprague Dawley Rat

In vitro metabolism of T-2 toxin by rat liver microsomes

1986 ◽  
Vol 34 (5) ◽  
pp. 865-868 ◽  
Author(s):  
Catherine A. Knupp ◽  
Steven P. Swanson ◽  
William B. Buck
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Metabolism ◽  
Rat Liver Microsomes

In vitro metabolism of cis- and trans-permethrin by rat liver microsomes, and its effect on estrogenic and anti-androgenic activities

2014 ◽  
Vol 37 (3) ◽  
pp. 996-1005 ◽  
Author(s):  
Satoko Tange ◽  
Nariaki Fujimoto ◽  
Naoto Uramaru ◽  
Kazumi Sugihara ◽  
Shigeru Ohta ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Metabolism ◽  
Rat Liver Microsomes ◽  
Cis And Trans

A non-michaelian behavior of the in vitro metabolism of the pentacyclic triterpene alfa and beta amyrins by employing rat liver microsomes

2013 ◽  
Vol 84 ◽  
pp. 14-19 ◽  
Author(s):  
Fernanda de Lima Moreira ◽  
Gustavo Henrique Bianco de Souza ◽  
Ivanildes Vasconcelos Rodrigues ◽  
Norberto Peporine Lopes ◽  
Anderson Rodrigo Moraes de Oliveira
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Metabolism ◽  
Rat Liver Microsomes ◽  
Pentacyclic Triterpene

scholarly journals Safety Assessment of Compounds after In Vitro Metabolic Conversion Using Zebrafish Eleuthero Embryos

2019 ◽  
Vol 20 (7) ◽  
pp. 1712 ◽  
Author(s):  
Arianna Giusti ◽  
Xuan-Bac Nguyen ◽  
Stanislav Kislyuk ◽  
Mélanie Mignot ◽  
Cecilia Ranieri ◽  
...  
Keyword(s):  
High Performance ◽  
Safety Assessment ◽  
Parent Compound ◽  
Liver Microsomes ◽  
Toxicity Testing ◽  
Rat Liver Microsomes ◽  
Metabolic Conversion ◽  
Toxic Potential

Zebrafish-based platforms have recently emerged as a useful tool for toxicity testing as they combine the advantages of in vitro and in vivo methodologies. Nevertheless, the capacity to metabolically convert xenobiotics by zebrafish eleuthero embryos is supposedly low. To circumvent this concern, a comprehensive methodology was developed wherein test compounds (i.e., parathion, malathion and chloramphenicol) were first exposed in vitro to rat liver microsomes (RLM) for 1 h at 37 °C. After adding methanol, the mixture was ultrasonicated, placed for 2 h at −20 °C, centrifuged and the supernatant evaporated. The pellet was resuspended in water for the quantification of the metabolic conversion and the detection of the presence of metabolites using ultra high performance liquid chromatography-Ultraviolet-Mass (UHPLC-UV-MS). Next, three days post fertilization (dpf) zebrafish eleuthero embryos were exposed to the metabolic mix diluted in Danieau’s medium for 48 h at 28 °C, followed by a stereomicroscopic examination of the adverse effects induced, if any. The novelty of our method relies in the possibility to quantify the rate of the in vitro metabolism of the parent compound and to co-incubate three dpf larvae and the diluted metabolic mix for 48 h without inducing major toxic effects. The results for parathion show an improved predictivity of the toxic potential of the compound.

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