ArticleScientific reports2017
Real-time in vivo imaging reveals localised Nrf2 stress responses associated with direct and metabolism-dependent drug toxicity.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- NQO1 as a predictor of response to adjuvant GemCap treatment for pancreatic cancer.Journal of the National Cancer Institute · 2026Article
- Limitations of acetaminophen as a reference hepatotoxin for the evaluation of in vitro liver models.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Biomarkers of NRF2 signalling: Current status and future challenges.Redox biology · 2024Review
- The evolving role of investigative toxicology in the pharmaceutical industry.Nature reviews. Drug discovery · 2023Review
- Intrabiliary infusion of naked DNA vectors targets periportal hepatocytes in mice.Molecular therapy. Methods & clinical development · 2022Article
- Role and Regulation of Hepatobiliary ATP-Binding Cassette Transporters during Chemical-Induced Liver Injury.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction.Acta pharmaceutica Sinica. B · 2021Review
- Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis.Scientific reports · 2021Article
- Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence.Genes & development · 2020Article
- Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models.Nature reviews. Drug discovery · 2020Review
- Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury.Nature materials · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
Abstract
The transcription factor Nrf2 coordinates an adaptive response to chemical and oxidative stress characterised by the upregulated expression of cytoprotective target genes. In order to understand the mechanistic relevance of Nrf2 as a marker of drug-induced stress it is important to know if this adaptive response is truly localised in the context of organ-specific drug toxicity. Here, we address this knowledge gap through real-time bioluminescence imaging of transgenic Nrf2-luciferase (Nrf2-luc) reporter mice following administration of the metabolism-dependent hepatotoxin acetaminophen (APAP) or the direct nephrotoxin cisplatin. We detected localised bioluminescence in the liver (APAP) and kidneys (cisplatin) in vivo and ex vivo, whilst qPCR, Taqman low-density array and immunoblot analysis of these tissues further revealed increases in the expression level of several endogenous Nrf2-regulated genes/proteins, including heme oxygenase 1 (Hmox1). Consistent with the toxic effects of APAP in the liver and cisplatin in the kidney, immunohistochemical analysis revealed the elevated expression of luciferase and Hmox1 in centrilobular hepatocytes and in tubular epithelial cells, respectively. In keeping with the role of reactive metabolite formation in APAP-induced chemical stress, both the hepatotoxicity and localised Nrf2-luc response were ameliorated by the cytochrome P450 inhibitor aminobenzotriazole. Together, these findings show that Nrf2 can reflect highly-localised cellular perturbations associated with relevant toxicological mechanisms.
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Registered trials
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