ArticleFrontiers in toxicology2022
Dissecting Drug-Induced Cytotoxicity and Metabolic Dysfunction in Conditionally Immortalized Human Proximal Tubule Cells.
Article in Frontiers in toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
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- Effects of Benzalkonium Chloride, a Preservative in Topical Drugs, on the Barrier Function of Human Corneal Epithelial Cells.Translational vision science & technology · 2025Article
- Antitumor Alkaloids in Tibetan Corydalis: Chemical Diversity and Pharmacological Insights.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- In vitro and preclinical evaluation of the antifungal activity of 6-methoxy-1 H-indole-2-carboxylic acid produced by Bacillus toyonensis strain OQ071612 formulated as nanosponge hydrogel.Microbial cell factories · 2025Article
- The Effects of Circadian Rhythm on Lead-Induced Toxicity in the DBC1.2 Olfactory Dark Basal Cell Line.Cells · 2025Article
- Encapsulation of Curcumin and Gemcitabine: Cytotoxic Effect and Mechanisms of Death in Lung Cancer.Advances in pharmacological and pharmaceutical sciences · 2025Article
- Nanosponge hydrogel of octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate of Alcaligenes faecalis.Applied microbiology and biotechnology · 2024Article
- Article
- Investigating the Effects of Chelidonic Acid on Oxidative Stress-Induced Premature Cellular Senescence in Human Skin Fibroblast Cells.Life (Basel, Switzerland) · 2024Article
- Improving the power of drug toxicity measurements by quantitative nuclei imaging.Cell death discovery · 2024Article
- Statins affect human iPSC-derived cardiomyocytes by interfering with mitochondrial function and intracellular acidification.Basic research in cardiology · 2024Article
- Dissecting Drug-Induced Cytotoxicity and Metabolic Dysfunction in Conditionally Immortalized Human Proximal Tubule Cells.Frontiers in toxicology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fourteen to 26 percent of all hospitalized cases of acute kidney injury are explained by drug-induced toxicity, emphasizing the importance of proper strategies to pre-clinically assess renal toxicity. The MTT assay is widely used as a measure of cell viability, but largely depends on cellular metabolic activity. Consequently, MTT as a single assay may not be the best way to assess cytotoxicity of compounds that reduce mitochondrial function and cellular metabolic activity without directly affecting cell viability. Accordingly, we aim to highlight the limitations of MTT alone in assessing renal toxicity of compounds that interfere with metabolic activity. Therefore, we compared toxic effects observed by MTT with a fluorescent assay that determines compromised plasma membrane permeability. Exposure of proximal tubule epithelial cells to nephrotoxic compounds reduced cellular metabolic activity concentration- and time-dependently. We show that compared to our fluorescence-based approach, assessment of cellular metabolic activity by means of MTT provides a composite readout of cell death and metabolic impairment. An approach independent of cellular metabolism is thus preferable when assessing cytotoxicity of compounds that induce metabolic dysfunction. Moreover, combining both assays during drug development enables a first discrimination between compounds having a direct or indirect mitochondrial toxic potential.
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