Evaluation of in vivo and in vitro models of toxicity by comparison of toxicogenomics data with the literature

Taškova, Katerina; Fontaine, Jean-Fred; Mrowka, Ralf; Andrade‐Navarro, Miguel A.

doi:10.1016/j.ymeth.2017.07.010

Cited by 8 publications

(7 citation statements)

References 19 publications

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“…Previous in vitro - in vivo research has often focused on identifying correlated genes, pathways, or gene ontology terms (Zhang et al, 2013; De Abrew et al, 2015; Sutherland et al, 2016; Van den Hof et al, 2017; Taškova et al, 2018). We have shown that DEGs do not show satisfactory in vitro - in vivo correlations, which makes selection of individual genes indicative of injury unreliable.…”

Section: Discussionmentioning

confidence: 99%

Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity

et al. 2019

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Consumers are exposed to thousands of chemicals with potentially adverse health effects. However, these chemicals will never be tested for toxicity because of the immense resources needed for animal-based (in vivo) toxicological studies. Today, there are no viable in vitro alternatives to these types of animal studies. To develop an in vitro approach, we investigated whether we could predict in vivo organ injuries in rats with the use of RNA-seq data acquired from tissues early in the development of toxicant-induced injury, by comparing gene expression data from RNA isolated from these rat tissues with those obtained from in vitro exposure of primary liver and kidney cells. We collected RNA-seq data from the liver and kidney tissues of Sprague-Dawley rats 8 or 24 h after exposing them to vehicle (control), low (25 mg/kg), or high (100 mg/kg) doses of thioacetamide, a known liver toxicant that promotes fibrosis; we used these doses and exposure times to cause only mild toxicant-induced injury. For the in vitro study, we treated two cell types from Sprague-Dawley rats, primary hepatocytes (vehicle; low, 0.025 mM; or high, 0.125 mM dose), and renal tube epithelial cells (vehicle; low, 0.125 mM; or high, 0.500 mM) dose) with the thioacetamide metabolite, thioacetamide-S-oxide, selecting in vitro doses and exposure times to recreate the early-stage toxicant-induced injury model that we achieved in vivo. RNA-seq data were collected 9 or 24 h after application of vehicle or thioacetamide-S-oxide. We found that our modular approach for the analysis of gene expression data derived from in vivo RNA-seq strongly correlated (R2 > 0.6) with the in vitro results at two different dose levels of thioacetamide/thioacetamide-S-oxide after 24 h of exposure. The top-ranked liver injury modules in vitro correctly identified the ensuing development of liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity

et al. 2019

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“…In this communication, we compared the P-gp binding sites across human, rat and mouse using molecular docking and protein-ligand interaction fingerprint analysis. The suitability of heterogeneous in vitro and in vivo data to model different aspects of human toxicity (or activity), that remained quite challenging, was recently demonstrated ( Taškova et al, 2018 ). However, transferability of human activity data for modeling in vitro and in vivo effects in rodents presents a contrasting perspective and has been so far unexplored.…”

Section: Discussionmentioning

confidence: 99%

Interspecies comparison of putative ligand binding sites of human, rat and mouse P-glycoprotein

Jain

Grandits

Ecker

2018

European Journal of Pharmaceutical Sciences

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Prior to the clinical phases of testing, safety, efficacy and pharmacokinetic profiles of lead compounds are evaluated in animal studies. These tests are primarily performed in rodents, such as mouse and rats. In order to reduce the number of animal experiments, computational models that predict the outcome of these studies and thus aid in prioritization of preclinical candidates are heavily needed. However, although computational models for human off-target interactions with decent quality are available, they cannot easily be transferred to rodents due to lack of respective data. In this study, we assess the transferability of human P-glycoprotein activity data for development of in silico models to predict in vivo effects in rats and mouse using a structure-based approach. P-glycoprotein (P-gp) is an ATP-dependent efflux transporter that transports xenobiotic compounds such as toxins and drugs out of cells and has a broad substrate and inhibitor specificity. Being mostly expressed at barriers, it influences the bioavailability of drugs and thus contributes also to toxicity. Comparison of the binding site interaction profiles of human, rat and mouse P-gp derived from docking studies with a set of common inhibitors suggests that the inhibitors share potentially similar binding modes. These findings encourage the use of in vitro human P-gp data for predicting in vivo effects in rodents and thus contributes to the 3Rs (Replace, Reduce and Refine) of animal experiments.

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“…Test systems, which can be used to assess the osteogenic potential of materials, can be categorized into in vivo and in vitro systems. In vivo test systems are the more accurate and complex systems of the two and reflect the subsequent application of the implant as close as possible [141,142]. Therefore, they are used in preclinical trials to assess the biofunctionality and biocompatibility of an implant in a living body with many complex systems influencing each other.…”

Section: Test Systems In Materials Evaluationmentioning

confidence: 99%

“…The advantages, limitations and applications of these systems are listed in Table 2. After the initial evaluation of the materials or implants, promising candidates are tested in in vivo models to obtain results that are more comparable to the human body and have a variety of biological mechanisms that are not implemented in in vitro models [141,142]. Animal models suitable for testing bone implants include mouse [145,146], rat [15,147], rabbit [57,148] and sheep [149,150].…”

Section: Test Systems In Materials Evaluationmentioning

confidence: 99%

“…Outcomes may differ between in vitro and in vivo experiments because many biological factors are not fully understood yet and are missing in some in vitro experiments. Therefore, a combination of both models is recommended [142,143]. Nevertheless, in vitro models are excellent for understanding an underlying mechanism or for analyzing a specific behavior because they are easy to manipulate and comprehend.…”

Section: Test Systems In Materials Evaluationmentioning

confidence: 99%

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Challenges in Bone Tissue Regeneration: Stem Cell Therapy, Biofunctionality and Antimicrobial Properties of Novel Materials and Its Evolution

Riester

Borgolte

Csuk

et al. 2020

IJMS

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An aging population leads to increasing demand for sustained quality of life with the aid of novel implants. Patients expect fast healing and few complications after surgery. Increased biofunctionality and antimicrobial behavior of implants, in combination with supportive stem cell therapy, can meet these expectations. Recent research in the field of bone implants and the implementation of autologous mesenchymal stem cells in the treatment of bone defects is outlined and evaluated in this review. The article highlights several advantages, limitations and advances for metal-, ceramic- and polymer-based implants and discusses the future need for high-throughput screening systems used in the evaluation of novel developed materials and stem cell therapies. Automated cell culture systems, microarray assays or microfluidic devices are required to efficiently analyze the increasing number of new materials and stem cell-assisted therapies. Approaches described in the literature to improve biocompatibility, biofunctionality and stem cell differentiation efficiencies of implants range from the design of drug-laden nanoparticles to chemical modification and the selection of materials that mimic the natural tissue. Combining suitable implants with mesenchymal stem cell treatment promises to shorten healing time and increase treatment success. Most research studies focus on creating antibacterial materials or modifying implants with antibacterial coatings in order to address the increasing number of complications after surgeries that are mostly caused by bacterial infections. Moreover, treatment of multiresistant pathogens will pose even bigger challenges in hospitals in the future, according to the World Health Organization (WHO). These antibacterial materials will help to reduce infections after surgery and the number of antibiotic treatments that contribute to the emergence of new multiresistant pathogens, whilst the antibacterial implants will help reduce the amount of antibiotics used in clinical treatment.

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Evaluation of in vivo and in vitro models of toxicity by comparison of toxicogenomics data with the literature

Cited by 8 publications

References 19 publications

Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity

Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity

Interspecies comparison of putative ligand binding sites of human, rat and mouse P-glycoprotein

Challenges in Bone Tissue Regeneration: Stem Cell Therapy, Biofunctionality and Antimicrobial Properties of Novel Materials and Its Evolution

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