ArticleCommunications biology2024
Activation of Nrf2/HO-1 signaling pathway exacerbates cholestatic liver injury.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Research progress on the protective effect and oxidative stress mechanism of rutin against liver injury (Review).Molecular medicine reports · 2026Review
- Esculin attenuates cholestatic liver injury and fibrosis in bile duct-ligated rats by modulating oxidative stress, inflammatory responses, and fibrogenic mediators.Molecular biology reports · 2026Article
- Varied Effects of Carnosine and an Antioxidant-Enriched Carnosine Supplement in Paracetamol-Induced Hepatotoxicity Model in Mice.Current issues in molecular biology · 2026Article
- Article
- Schisandrol B protects against lithocholic acid-induced cholestatic liver injury in mice through mitochondrial biogenesis.Chinese medicine · 2026Article
- Article
- Loss of energy homeostasis contributes to hepatic damage development in sickle cell disease.Molecular metabolism · 2026Article
- Article
- Mitochondrial DNA drives NLRP3-IL-1β axis activation in microglia by binding to NLRP3, leading to neurodegeneration in Parkinson's disease models.Cell death & disease · 2026Article
- Targeting the JAK/STAT pathway with isoliquiritigenin in ovarian cancer: molecular mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- Under Chronic, High-Dose Administration of Wenjing Decoction, the Activation of the Hepatic Nrf2/HO-1 Pathway Mediates Increased Bilirubin Levels and Associated Reversible Neurologic Dysfunction in Mice.Journal of toxicology · 2026Article
- An Association between Bilirubin and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: An Effect Modification by Nrf2 Polymorphisms.Current diabetes reviews · 2026Article
- Computational design, synthesis,RSC advances · 2025Article
- Gamma-aminobutyric acid attenuates cortisol-induced damage in human colorectal adenocarcinoma cells via Nrf2 signaling.Die Naturwissenschaften · 2025Article
- Aloesin activates Nrf2 signaling to attenuate obesity-associated oxidative stress and hepatic steatosis in high-fat diet-fed rats.Scientific reports · 2025Article
- Novel prolyl endopeptidase inhibitor fromRSC advances · 2025Article
- Sex-specific metabolic responses to high-fat diet in mice with NOX4 deficiency.Redox biology · 2025Article
- Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.Medical oncology (Northwood, London, England) · 2025Review
- T-2 Toxin-Induced Hepatotoxicity in HepG2 Cells Involves the Inflammatory and Nrf2/HO-1 Pathways.Toxins · 2025Article
- A hepatoprotective experiment on taro vegetable (Colocasia esculenta (L.) Schott) flower employing animal models by mitigating oxidative stress.Animal models and experimental medicine · 2025Article
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear factor erythroid 2-related factor-2 (Nrf2) antioxidant signaling is involved in liver protection, but this generalization overlooks conflicting studies indicating that Nrf2 effects are not necessarily hepatoprotective. The role of Nrf2/heme oxygenase-1 (HO-1) in cholestatic liver injury (CLI) remains poorly defined. Here, we report that Nrf2/HO-1 activation exacerbates liver injury rather than exerting a protective effect in CLI. Inhibiting HO-1 or ameliorating bilirubin transport alleviates liver injury in CLI models. Nrf2 knockout confers hepatoprotection in CLI mice, whereas in non-CLI mice, Nrf2 knockout aggravates liver damage. In the CLI setting, oxidative stress activates Nrf2/HO-1, leads to bilirubin accumulation, and impairs mitochondrial function. High levels of bilirubin reciprocally upregulate the activation of Nrf2 and HO-1, while antioxidant and mitochondrial-targeted SOD2 overexpression attenuate bilirubin toxicity. The expression of Nrf2 and HO-1 is elevated in serum of patients with CLI. These results reveal an unrecognized function of Nrf2 signaling in exacerbating liver injury in cholestatic disease.
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