ArticleCell death & disease2020
(+)-Clausenamide protects against drug-induced liver injury by inhibiting hepatocyte ferroptosis.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 107 citations in OpenAlex.
- Putative Modulation of OATP1A2 and P-gp Expression at the Blood-Brain Barrier by Nrf2-PXR: An Associative Hypothesis for Amyloid-β Transport in Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Gallium-Doped MXene Nanozymes Protect Liver Through Multi-Death Pathway Blockade and Hepatocyte Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Response mechanism of hepatorenal metabolic barrier function to drugs and environmental poisons and intervention strategy of natural products.Frontiers in pharmacology · 2026Review
- Dual Roles of Natural Products in Regulating Ferroptosis in Acute and Chronic Liver Diseases: A Review.Oxidative medicine and cellular longevity · 2026Review
- LF3 exerts anti-osteosarcoma effects through Wnt signaling inhibition-coupled ferroptosis induction viaFrontiers in oncology · 2026Article
- Targeting ferroptosis as a therapeutic strategy for hepatotoxicity.Toxicology reports · 2025Review
- Decoding the regulatory role of noncoding RNAs in biological and vascular calcification.Molecular biology reports · 2025Review
- "Weibing" in traditional Chinese medicine-biological basis and mathematical representation of disease-susceptible state.Acta pharmaceutica Sinica. B · 2025Review
- Identification of Food-Derived Electrophilic Chalcones as Nrf2 Activators Using Comprehensive Virtual Screening Techniques.Antioxidants (Basel, Switzerland) · 2025Article
- Astaxanthin Mitigates 5-Fluorouracil-Induced Hepatotoxicity and Oxidative Stress in Male Rats.Nutrients · 2025Article
- Natural Polyphenol-Mediated Inhibition of Ferroptosis Alleviates Oxidative Damage and Inflammation in Acute Liver Injury.Biomaterials research · 2025Article
- [Ferroptosis and liver diseases].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- MCL restrained ROS/AKT/ASAH1 pathway to therapy tamoxifen resistance breast cancer by stabilizing NRF2.Cell proliferation · 2024Article
- Drug-induced oxidative stress actively prevents caspase activation and hepatocyte apoptosis.Cell death & disease · 2024Article
- Targeting both ferroptosis and pyroptosis may represent potential therapies for acute liver failure.World journal of gastroenterology · 2024Article
- Role of Gut Microecology in the Pathogenesis of Drug-Induced Liver Injury and Emerging Therapeutic Strategies.Molecules (Basel, Switzerland) · 2024Review
- Metabolomics reveals ascorbic acid inhibits ferroptosis in hepatocytes and boosts the effectiveness of anti-PD1 immunotherapy in hepatocellular carcinoma.Cancer cell international · 2024Article
- Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2024Review
- Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes.World journal of gastroenterology · 2024Article
- Review
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug-induced liver injury is the major cause of acute liver failure. However, the underlying mechanisms seem to be multifaceted and remain poorly understood, resulting in few effective therapies. Here, we report a novel mechanism that contributes to acetaminophen-induced hepatotoxicity through the induction of ferroptosis, a distinctive form of programmed cell death. We subsequently identified therapies protective against acetaminophen-induced liver damage and found that (+)-clausenamide ((+)-CLA), an active alkaloid isolated from the leaves of Clausena lansium (Lour.) Skeels, inhibited acetaminophen-induced hepatocyte ferroptosis both in vivo and in vitro. Consistently, (+)-CLA significantly alleviated acetaminophen-induced or erastin-induced hepatic pathological damages, hepatic dysfunctions and excessive production of lipid peroxidation both in cultured hepatic cell lines and mouse liver. Furthermore, treatment with (+)-CLA reduced the mRNA level of prostaglandin endoperoxide synthase 2 while it increased the protein level of glutathione peroxidase 4 in hepatocytes and mouse liver, confirming that the inhibition of ferroptosis contributes to the protective effect of (+)-CLA on drug-induced liver damage. We further revealed that (+)-CLA specifically reacted with the Cys-151 residue of Keap1, which blocked Nrf2 ubiquitylation and resulted in an increased Nrf2 stability, thereby leading to the activation of the Keap1-Nrf2 pathway to prevent drug-induced hepatocyte ferroptosis. Our studies illustrate the innovative mechanisms of acetaminophen-induced liver damage and present a novel intervention strategy to treat drug overdose by using (+)-CLA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.