Jekyll and Hyde: nuclear receptors ignite and extinguish hepatic oxidative milieu

Anushna Sen1, Sayeepriyadarshini Anakk1

  • 1Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Insights

Nuclear receptors (NRs) regulate gene networks and physiological responses. Their interaction with Nrf2 influences oxidative stress, offering potential therapeutic targets for liver diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Hepatology

Background:

  • Oxidative stress is a key factor in liver disease development.
  • Nuclear receptors (NRs) are crucial transcription factors involved in various physiological processes.
  • Nrf2 is a master regulator of cellular antioxidant defenses.

Purpose of the Study:

  • To explore the intricate crosstalk between nuclear receptors and the Nrf2 antioxidant pathway.
  • To discuss how NRs modulate oxidative stress in the context of diet, pollutants, and drug-induced liver injury.
  • To investigate the potential repurposing of FDA-approved NR-targeting drugs for managing reactive oxygen species (ROS).

Main Methods:

  • Literature review and synthesis of existing research on NRs, Nrf2, and oxidative stress.
  • Analysis of how dietary components, environmental pollutants, and xenobiotics affect NR activity and oxidative balance.
  • Discussion of the dual role of NRs in either exacerbating or mitigating liver toxicity.

Main Results:

  • NRs significantly influence the cellular oxidative milieu through modulation of reductive processes.
  • NR activity and expression are regulated by diet and xenobiotics, indicating a feedback loop.
  • NRs exhibit context-dependent effects on liver toxicity and oxidative damage.

Conclusions:

  • The interplay between NRs and Nrf2 presents a promising avenue for therapeutic intervention in liver diseases.
  • Understanding NR modulation of oxidative stress can guide the repurposing of existing drugs to combat ROS.
  • Targeting NRs offers a potential strategy to ameliorate liver injury caused by various environmental and chemical insults.

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