Real-time in vivo imaging reveals localised Nrf2 stress responses associated with direct and metabolism-dependent drug toxicity.

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 analysi

SUBMITTER: Forootan SS 

PROVIDER: S-EPMC5700176 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature