Gut microbiota depletion and FXR inhibition exacerbates zonal hepatotoxicity of sunitinib DOI Creative Commons

Qi Zhao,

Ying‐Mei Lu, Jingyi Duan

и другие.

Theranostics, Год журнала: 2024, Номер 14(18), С. 7219 - 7240

Опубликована: Окт. 28, 2024

Rationale: Sunitinib is a small-molecule tyrosine kinase inhibitor associated with the side-effect of liver injury. The impaired cell type in and hepatotoxicity mechanisms still unclear. Methods: Spatial metabolomics, transmission electron microscopy, immunofluorescence co-staining, isolation bile duct cells sinusoidal endothelial (LSECs) were used to evaluate zonated sunitinib. Farnesoid X receptor (FXR) conditional knockout mice, metagenomics analysis, bacteria clearance, bacterial culture, Parabacteroides distasonis 3-oxolithocholic acid supplementation Results: Phenotype analysis found that hepatic autophagy, apoptosis, mitochondrial injury observed vivo or vitro after sunitinib treatment. By using spatial metabolomics LSECs, drug toxicity was around portal vein. Hepatocytes, cells, LSECs damaged FXR inhibition gut microbiota depletion aggravated sunitinib-induced For diurnal variation, enhanced at night compared day, participated circadian rhythmic induced by Conclusions: Our data suggested activation may be improve hepatotoxicity.

Язык: Английский

HLA-B*35:01-mediated activation of emodin-specific T cells contributes to Polygonum multiflorum Thunb. -induced liver injury in mice DOI
Xiangchang Zeng, Chaopeng Li, Yating Liu

и другие.

Journal of Ethnopharmacology, Год журнала: 2024, Номер 334, С. 118523 - 118523

Опубликована: Июль 4, 2024

Язык: Английский

Процитировано

1

Desorption Electrospray Ionization-Mass Spectrometry Imaging-Based Spatial Metabolomics for Visualizing and Comparing Ginsenosides and Lipids among Multiple Parts and Positions of the Panax ginseng Root DOI
Hongda Wang, Li‐Li Hong, Feifei Yang

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 2, 2024

Ginsenosides and lipids are both bioactive ingredients for ginseng. Targeting these two categories of components, this study was designed to develop desorption electrospray ionization-mass spectrometry imaging approaches spatial metabolomics strategies, achieving the visualization differentiation among different parts Panax ginseng root (e.g., rhizome, main root, lateral fibrous adventitious root). Potential chemical markers were identified by searching an in-house ginsenoside library online Lipid Maps database, together with high-resolution MS2 data analysis. Six ginsenosides 11 diagnostic differentiate five P. root. Additionally, three 20 as differential six positions High-abundance malonyl- oleanolic acid-ginsenosides observed in rhizome. These results assist understanding accumulation molecules all through ginseng, which can benefit its quality control rational use.

Язык: Английский

Процитировано

1

Current Evidence: Application of Metabolomic Approaches to Reveal Toxic Effect of Chemicals and Herbal Medicines DOI Creative Commons
Xia Li, Junling Ren, Taiping Li

и другие.

Natural Product Communications, Год журнала: 2024, Номер 19(6)

Опубликована: Июнь 1, 2024

Humans are often exposed to a variety of toxic substances (including some drugs, herbs, environmental pollutants); all these heterologous can result in metabolic changes organism. Clarifying their details will help understand the beneficial and effects those substances. Traditional toxicology research tends focus on doses time rather than mechanisms detoxification methods. Compared with other omics methods, metabolomics has unique, dynamic, phenotypic characteristics. Similarly, link interaction between genes environment; it represents both downstream output genome upstream input environment, reflects interactions biological system stimulation. It highlighting not only but also closely related phenotype events, which is widely employed studies presently. Therefore, strengthening toxicological based better action Thus, present review systematically summarized discussed current application status approaches toxicology, might contribute provide deeper understanding processes toxicity caused by chemicals herbal medicines, thereby reducing occurrence damage providing technical reference for research.

Язык: Английский

Процитировано

0

Comprehensive spatial distribution profiling of bioactive emodin in mouse organs using mass spectrometry imaging DOI Open Access

Si-Qi Han,

Xiao-Kang Fu,

Wei Ha

и другие.

Analytical Sciences, Год журнала: 2024, Номер 40(11), С. 2063 - 2073

Опубликована: Авг. 13, 2024

Emodin is an important anthraquinone compound with good anti-inflammatory activity in Chinese traditional medicine rhubarb. Detailed spatial distribution information bio-tissues plays role revealing the pharmacodynamics, toxicology and chemical mechanism of emodin. Herein, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) analytical method was established to obtain on temporal changes emodin multiple mouse tissue sections (heart, liver, spleen, lung, kidney, brain) after intraperitoneal injection mice. The measurements were accomplished negative ion mode range m/z 250-285 Da a resolution 40 µm. It found that predominantly distributed arteriolar vascular region heart, capsule cortex kidney. Moreover, MALDI-TOF-MSI result implied might be brain. These more detailed provides significant reference for investigating action emodin, which cannot obtained from conventional LC-MS analysis. trend results analysis agreed ultra-performance liquid chromatography/tandem (UPLC-MS/MS) well, demonstrating complementarity reliability method. Our work provided label-free molecular investigate precise various organs, prove great potential studying effective substances

Язык: Английский

Процитировано

0

Gut microbiota depletion and FXR inhibition exacerbates zonal hepatotoxicity of sunitinib DOI Creative Commons

Qi Zhao,

Ying‐Mei Lu, Jingyi Duan

и другие.

Theranostics, Год журнала: 2024, Номер 14(18), С. 7219 - 7240

Опубликована: Окт. 28, 2024

Rationale: Sunitinib is a small-molecule tyrosine kinase inhibitor associated with the side-effect of liver injury. The impaired cell type in and hepatotoxicity mechanisms still unclear. Methods: Spatial metabolomics, transmission electron microscopy, immunofluorescence co-staining, isolation bile duct cells sinusoidal endothelial (LSECs) were used to evaluate zonated sunitinib. Farnesoid X receptor (FXR) conditional knockout mice, metagenomics analysis, bacteria clearance, bacterial culture, Parabacteroides distasonis 3-oxolithocholic acid supplementation Results: Phenotype analysis found that hepatic autophagy, apoptosis, mitochondrial injury observed vivo or vitro after sunitinib treatment. By using spatial metabolomics LSECs, drug toxicity was around portal vein. Hepatocytes, cells, LSECs damaged FXR inhibition gut microbiota depletion aggravated sunitinib-induced For diurnal variation, enhanced at night compared day, participated circadian rhythmic induced by Conclusions: Our data suggested activation may be improve hepatotoxicity.

Язык: Английский

Процитировано

0