| Title |
Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures
|
|---|---|
| Published in |
Archives of Toxicology, May 2018
|
| DOI | 10.1007/s00204-018-2214-z |
| Pubmed ID | |
| Authors |
Robim M. Rodrigues, Laxmikanth Kollipara, Umesh Chaudhari, Agapios Sachinidis, René P. Zahedi, Albert Sickmann, Annette Kopp-Schneider, Xiaoqi Jiang, Hector Keun, Jan Hengstler, Marlies Oorts, Pieter Annaert, Eef Hoeben, Eva Gijbels, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, Mathieu Vinken |
| Abstract |
Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event. Transcriptomics results further showed several gene changes related to the activation of the nuclear farnesoid X receptor. Induction of oxidative stress and inflammation were also observed. Metabolomics analysis indicated changes in the abundance of specific endogenous metabolites related to mitochondrial impairment. The outcome of this study may assist in the further optimization of adverse outcome pathway constructs that mechanistically describe the processes involved in cholestatic liver injury. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 56 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 13 | 23% |
| Student > Master | 9 | 16% |
| Student > Bachelor | 5 | 9% |
| Student > Doctoral Student | 3 | 5% |
| Researcher | 3 | 5% |
| Other | 4 | 7% |
| Unknown | 19 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 13 | 23% |
| Medicine and Dentistry | 5 | 9% |
| Biochemistry, Genetics and Molecular Biology | 4 | 7% |
| Agricultural and Biological Sciences | 3 | 5% |
| Materials Science | 2 | 4% |
| Other | 7 | 13% |
| Unknown | 22 | 39% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 May 2018.
All research outputs
#20,742,744
of 23,344,526 outputs
Outputs from Archives of Toxicology
#2,395
of 2,669 outputs
Outputs of similar age
#288,348
of 327,646 outputs
Outputs of similar age from Archives of Toxicology
#27
of 30 outputs
Altmetric has tracked 23,344,526 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,669 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 327,646 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.