Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integrated metabolic models for xenobiotic induced mitochondrial toxicity in skeletal muscle

ABSTRACT: Integrated metabolic models for xenobiotic induced mitochondrial toxicity in skeletal muscle

PROVIDER: PRJNA395691 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Integrated metabolic models for xenobiotic induced mitochondrial toxicity in skeletal muscle (compound 197 experiments)

Project description:There is a need for robust in vitro models to sensitively capture skeletal muscle adverse toxicities early in the research and development of novel xenobiotics. To this end, an in vitro rat skeletal muscle model (L6) was used to study the translation of transcriptomics data generated from an in vivo rat model. Novel sulfonyl isoxazoline herbicides were associated with skeletal muscle toxicity in an in vivo rat model. Gene expression pathway analysis on skeletal muscle tissues taken from in vivo repeat dose studies identified enriched pathways associated with mitochondrial dysfunction, oxidative stress, energy metabolism, protein regulation and cell cycle. Mitochondrial dysfunction and oxidative stress were further explored in an in vitro L6 model. This model demonstrated that the sulfonyl isoxazoline compounds induced mitochondrial dysfunction, mitochondrial superoxide production and apoptosis. These in vitro findings accurately concurred with the in vivo transcriptomics data, thereby confirming the ability of the L6 skeletal muscle model to identify relevant in vivo mechanisms of xenobiotic-induced toxicity. Moreover, these results highlight the sensitivity of the L6 galactose media model to study mitochondrial perturbation associated with skeletal muscle toxicity; this model may be utilised to rank the potency of novel xenobiotics upon further validation.

2017-07-26 | GSE101845 | GEO

Integrated metabolic models for xenobiotic induced mitochondrial toxicity in skeletal muscle (compound 177 experiments)

2017-07-26 | GSE101844 | GEO

Integrated metabolic models for xenobiotic induced mitochondrial toxicity in skeletal muscle.

Project description:There is a need for robust in vitro models to sensitively capture skeletal muscle adverse toxicities early in the research and development of novel xenobiotics. To this end, an in vitro rat skeletal muscle model (L6) was used to study the translation of transcriptomics data generated from an in vivo rat model. Novel sulfonyl isoxazoline herbicides were associated with skeletal muscle toxicity in an in vivo rat model. Gene expression pathway analysis on skeletal muscle tissues taken from in vivo repeat dose studies identified enriched pathways associated with mitochondrial dysfunction, oxidative stress, energy metabolism, protein regulation and cell cycle. Mitochondrial dysfunction and oxidative stress were further explored using in vitro L6 metabolic models. These models demonstrated that the sulfonyl isoxazoline compounds induced mitochondrial dysfunction, mitochondrial superoxide production and apoptosis. These in vitro findings accurately concurred with the in vivo transcriptomics data, thereby confirming the ability of the L6 skeletal muscle models to identify relevant in vivo mechanisms of xenobiotic-induced toxicity. Moreover, these results highlight the sensitivity of the L6 galactose media model to study mitochondrial perturbation associated with skeletal muscle toxicity; this model may be utilised to rank the potency of novel xenobiotics upon further validation.

| S-EPMC5610037 | biostudies-literature

Integrated metabolic models for xenobiotic induced mitochondrial toxicity in skeletal muscle

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-07-26 | GSE101847 | GEO

A molecular insight into fluoride toxicity in skeletal muscle using invitro C2C12 and in vivo C57BL/6 mice models

Project description:Fluoride toxicity in multiple organs has been extensively reported in several decades of research. In-depth study coverage is available on teeth and bone tissues. But studies addressing skeletal muscle fluorosis are scanty. C57BL/6 mice were provided with sodium fluoride in drinking water for 60 days. Histological analysis, primary culture of skeletal muscle was performed. Protein expressions were analyzed by Immunocytochemistry, qRT-PCR, and western blotting techniques. Proteomic approach was considered to overview the entire proteome response. Exposure to sodium fluoride resulted in the loss of body weight in C57BL/6 mice. The compactness of the myofibre arrangement was distorted due to the treatment. Major reduction of contractile proteins such as actinin, troponin, and myosin further loss of mitochondrial proteins were confirmed by proteomic approach. Sodium fluoride treatment altered mitochondrial function. Further, loss of contractile proteins triggered skeletal muscle weakness.

2023-03-11 | PXD035014 | Pride

Rattus norvegicus

Project description:Integrated metabolic models for xenobiotic induced mitochondrial toxicity in skeletal muscle (compound 177 experiments)

| PRJNA395695 | ENA

Rattus norvegicus

Project description:Integrated metabolic models for xenobiotic induced mitochondrial toxicity in skeletal muscle (compound 197 experiments)

| PRJNA395696 | ENA

Transcription profiling of Drosophila melanogaster Canton S DHR96 mutants treated with the xenobiotic phenobarbital, DHR96 is an ortholog of xenobiotic nuclear receptors PXR and CAR, and plays a role in mediating xenobiotic responses in Drosophila

Project description:Phenobarbital is a well studied xenobiotic compound. In this study, we describe the genomic responses in fruit flies and examine whether animals mutant for DHR96, an ortholog of xenobiotic nuclear receptors PXR and CAR, plays a role in mediating xenobiotic responses in Drosophila. Experiment Overall Design: Canton S is a commonly used wild type control strain for xenobiotic studies. Wild type or DHR96 mutant flies were starved overnight and then exposed to either sucrose alone or sucrose supplemented with 0.3% Phenobarbital.

2007-11-11 | E-GEOD-5096 | biostudies-arrayexpress

Shifted Metabolic Bias in Livers of Mice Lacking Hepatocytic Thioredoxin Reductase-1 Protects Against Acetaminophen Toxicity

Project description:Genetic disruption of thioredoxin reductase 1 protects against acetaminophen (APAP) toxicity. To determine the role of the thioredoxin system on xenobiotic metabolism we challeneged wildtype and txnrd1liver-null mice with acetaminophen.

2013-06-08 | GSE37874 | GEO

Benzene toxicity

Project description:Benzene toxicity

| PRJNA641636 | ENA