In Vitro Liver Toxicity Testing of Chemicals: A Pragmatic Approach

Tabernilla, Andrés; Rodrigues, Bruna dos Santos; Pieters, Alanah; Caufriez, Anne; Leroy, Kaat; Campenhout, Raf Van; Cooreman, Axelle; Gomes, Ana Rita Coelho; Arnesdotter, Emma; Gijbels, Eva; Vinken, Mathieu

doi:10.3390/ijms22095038

Cited by 22 publications

(15 citation statements)

References 384 publications

(581 reference statements)

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“…These are often detected with microscopy techniques or flow cytometry. Absolute lipid quantification assays are also used to determine intracellular lipid levels, in which various multi-step protocols are used to extract and quantify the total lipid content, either with high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) methods or fluorimetric-based and colorimetric-based assays [ 297 , 298 , 299 , 300 ].…”

Section: Experimental Models and Methods To Study Hepatic Mitochondri...mentioning

confidence: 99%

Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods

Mihajlovic

Vinken

2022

IJMS

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One of the major mechanisms of drug-induced liver injury includes mitochondrial perturbation and dysfunction. This is not a surprise, given that mitochondria are essential organelles in most cells, which are responsible for energy homeostasis and the regulation of cellular metabolism. Drug-induced mitochondrial dysfunction can be influenced by various factors and conditions, such as genetic predisposition, the presence of metabolic disorders and obesity, viral infections, as well as drugs. Despite the fact that many methods have been developed for studying mitochondrial function, there is still a need for advanced and integrative models and approaches more closely resembling liver physiology, which would take into account predisposing factors. This could reduce the costs of drug development by the early prediction of potential mitochondrial toxicity during pre-clinical tests and, especially, prevent serious complications observed in clinical settings.

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Section: Experimental Models and Methods To Study Hepatic Mitochondri...mentioning

confidence: 99%

Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods

Mihajlovic

Vinken

2022

IJMS

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“…Chemical-induced hepatotoxicity can manifest in several prominent ways, such as cholestasis, steatosis, fibrosis, and cancer, and is a major reason for discontinuation of drug development or withdrawal of drugs from the market. It also is a concern for other sectors, including the cosmetics area ( Tabernilla et al, 2021 ). In this respect, it remains challenging to detect and predict chemical-induced liver toxicity.…”

Section: The Use Of Aops For In Vitro Prediction O...mentioning

confidence: 99%

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks

Hoffmann

Aiassa

Angrish

et al. 2022

ALTEX

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Although emissions of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been dramatically reduced, the persistence and bioaccumulation of these chemicals result in detectable levels in the U.S. population. Despite declining emissions, there is continued widespread exposure to both chemicals and a number of studies have reported potential PFOA-and PFOS-associated immunotoxicity in both humans and non-human animals. The NTP conducted a systematic review to evaluate the evidence on exposure to PFOS or PFOA and immune-related health effects to determine whether exposure to either chemical is associated with immunotoxicity for humans. The literature search and screening process identified 33 human studies, 93 animal studies, and 27 in vitro/mechanistic studies relevant for addressing the objective. The health effects data for PFOA and PFOS were considered separately in developing hazard identification conclusions. Conclusions for each chemical were reached by integrating evidence from human and animal studies with consideration of any mechanistic data. PEER REVIEW OF THE DRAFT NTP MONOGRAPHPeer review of the draft NTP Monograph was conducted by an ad hoc expert panel in a public meeting held July 19, 2016, at the National Institute of Environmental Health Sciences, Research triangle park and via WebEx (see http://ntp.niehs.nih.gov/go/37090 for meeting materials and peer review report). The selection of panel members and conduct of the peer review were performed in accordance with the Federal Advisory Committee Act and Federal policies and regulations. The panel members served as independent scientists, not as representatives of any institution, company, or governmental agency. In this capacity, panel members had two major responsibilities in reviewing the draft NTP Monograph:(1) to determine whether the scientific information cited in the draft monograph was technically correct and clearly stated, and whether NTP has objectively presented and assessed the scientific evidence;(2) to determine whether the scientific evidence presented in the draft monograph supported the NTP's conclusions regarding whether immunotoxicity is associated with exposure to PFOA or PFOS.The panel agreed with the draft conclusions that PFOA and PFOS are both presumed to be immune hazards to humans; however, they recommended changing the level of evidence conclusion for hypersensitivity-related outcomes for the animal body of evidence from "high" to "moderate". NTP concurred with this recommendation. Comments from the peer reviewers and written public comments were considered during finalization of the document.

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“…LDH is released to the culture medium after membrane disruption in dead cells. LDH catalyzes the conversion of lactate to pyruvate and the simultaneous conversion of NAD + to NADH in the first step [ 84 , 85 , 86 ]. The produced NADH is then used in the following step to reduce the tetrazolium salt into formazan which is measured colorimetrically.…”

Section: Viability Testmentioning

confidence: 99%

DNA Dyes—Highly Sensitive Reporters of Cell Quantification: Comparison with Other Cell Quantification Methods

Ligasová

Koberna

2021

Molecules

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Cell quantification is widely used both in basic and applied research. A typical example of its use is drug discovery research. Presently, plenty of methods for cell quantification are available. In this review, the basic techniques used for cell quantification, with a special emphasis on techniques based on fluorescent DNA dyes, are described. The main aim of this review is to guide readers through the possibilities of cell quantification with various methods and to show the strengths and weaknesses of these methods, especially with respect to their sensitivity, accuracy, and length. As these methods are frequently accompanied by an analysis of cell proliferation and cell viability, some of these approaches are also described.

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In Vitro Liver Toxicity Testing of Chemicals: A Pragmatic Approach

Cited by 22 publications

References 384 publications

Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods

Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks

DNA Dyes—Highly Sensitive Reporters of Cell Quantification: Comparison with Other Cell Quantification Methods

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