ArticleToxicological sciences : an official journal of the Society of Toxicology2015
Quantification of Low-Level Drug Effects Using Real-Time, in vitro Measurement of Oxygen Consumption Rate.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Article
- Real-Time Monitoring of Oxygen-Consumption Rate in Mouse Liver Slices Incubated in Organ-on-a-Chip Devices.Analytical chemistry · 2024Article
- Comprehensive GC-MS Measurement of Amino Acids, Metabolites, and Malondialdehyde in Metformin-Associated Lactic Acidosis at Admission and during Renal Replacement Treatment.Journal of clinical medicine · 2024Article
- Article
- Hypertonicity during a rapid rise in D-glucose mediates first-phase insulin secretion.Frontiers in endocrinology · 2024Article
- A versatile pumpless multi-channel fluidics system for maintenance and real-time functional assessment of tissue and cells.Cell reports methods · 2023Article
- Maintaining and Assessing Various Tissue and Cell Types of the Eye Using a Novel Pumpless Fluidics System.Journal of visualized experiments : JoVE · 2023Article
- Aerobic Glycolysis in Photoreceptors Supports Energy Demand in the Absence of Mitochondrial Coupling.Advances in experimental medicine and biology · 2023Article
- Succinate metabolism in the retinal pigment epithelium uncouples respiration from ATP synthesis.Cell reports · 2022Article
- Fluidics system for resolving concentration-dependent effects of dissolved gases on tissue metabolism.eLife · 2021Article
- Unveiling the contribution of the reproductive system of individual Caenorhabditis elegans on oxygen consumption by single-point scanning electrochemical microscopy measurements.Analytica chimica acta · 2021Article
- Increasing metformin concentrations and its excretion in both rat and porcine ex vivo normothermic kidney perfusion model.BMJ open diabetes research & care · 2020Article
- Metformin lowers glucose 6-phosphate in hepatocytes by activation of glycolysis downstream of glucose phosphorylation.The Journal of biological chemistry · 2020Article
- The TGFβ1 Receptor Antagonist GW788388 Reduces JNK Activation and Protects Against Acetaminophen Hepatotoxicity in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Article
- Metformin-associated lactic acidosis: Moving towards a new paradigm?Diabetes, obesity & metabolism · 2017Article
- A method for high-throughput functional imaging of single cells within heterogeneous cell preparations.Scientific reports · 2016Article
- BaroFuse, a novel pressure-driven, adjustable-throughput perfusion system for tissue maintenance and assessment.Heliyon · 2016Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
There is a general need to detect toxic effects of drugs during preclinical screening. We propose that increased sensitivity of xenobiotics toxicity combined with improved in vitro physiological recapitulation will more accurately assess potentially toxic perturbations of cellular biochemistry that are near in vivo pharmacological exposure levels. Importantly, measurement of such cytopathologies avoids activating mechanisms mediating toxicity at suprapharmacologic levels not relevant to in vivo effects. We present a sensitive method to measure changes in oxygen consumption rate (OCR), a well-established parameter reflecting a potential hazard, in response to exposure to pharmacologic levels of drugs using a flow culture system and state of the art oxygen sensing system. We tested metformin and acetaminophen on rat liver slices to illustrate the method. The features of the method include continuous and very stable measurement of OCR over the course of 48 h in liver slices in a continuous flow chamber with the ability to resolve changes as small as 0.3%/h. Kinetic modeling of metformin inhibition of OCR over a wide range of concentrations revealed both a slow and fast mechanism, where the fast mechanism activated only at concentrations above 0.6 mM. For both drugs, small amounts of inhibition were reversible, but higher decrements were irreversible. Overall the study highlights the advantages of measuring low-level toxicity so as to avoid the common extrapolations made about drug toxicity based on effects of drugs tested at suprapharmacologic levels.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.