ArticleRedox biology2020
Diclofenac impairs autophagic flux via oxidative stress and lysosomal dysfunction: Implications for hepatotoxicity.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 96 citations in OpenAlex.
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- Peroxiredoxin Ⅲ safeguards cardiac function against doxorubicin by regulating mitochondrial quality control via HRedox biology · 2026Article
- Amelioration of gentamicin-induced acute kidney injury by trifluoperazine: in vivo mechanistic insights.Scientific reports · 2026Article
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- Unlocking the Anti-Inflammatory Potential of Sourdough: Phytochemical Profile, Functional Investigation, and Molecular Docking Insights into Key Bioactive Compounds.Plant foods for human nutrition (Dordrecht, Netherlands) · 2025Article
- Cyclooxygenase-2/prostaglandin E2 inhibition remodulated photodynamic therapy-associated immunosuppression for enhanced cancer immunotherapy.Materials today. Bio · 2025Article
- Evaluating diclofenac's risks in COVID-19: strategies for mitigating adverse outcomes.Inflammopharmacology · 2025Article
- Acupotomy Ameliorates KOA Related Chondrocyte Premature Senescence Through YAP/FOXD1 Pathway.Journal of pain research · 2025Article
- Advances in drug-induced liver injury research: in vitro models, mechanisms, omics and gene modulation techniques.Cell & bioscience · 2024Review
- PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through TXNIP-mediated oxidative stress.Cellular & molecular biology letters · 2024Article
- The Influence of Stress and Binge-Patterned Alcohol Drinking on Mouse Skeletal Muscle Protein Synthesis and Degradation Pathways.Biomolecules · 2024Article
- Mitochondrial HAntioxidants (Basel, Switzerland) · 2023Article
- The Phytochemical Profiling, In Vitro Antioxidant, and Hepatoprotective Activity ofInternational journal of molecular sciences · 2023Article
- Hepatoprotective and nephroprotective effects ofVeterinary world · 2023Article
- The CREG1-FBXO27-LAMP2 axis alleviates diabetic cardiomyopathy by promoting autophagy in cardiomyocytes.Experimental & molecular medicine · 2023Article
- Mefenamic Acid-Upregulated Nrf2/SQSTM1 Protects Hepatocytes against Oxidative Stress-Induced Cell Damage.Toxics · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with various side effects, including cardiovascular and hepatic disorders. Studies suggest that mitochondrial damage and oxidative stress are important mediators of toxicity, yet the underlying mechanisms are poorly understood. In this study, we identified that some NSAIDs, including diclofenac, inhibit autophagic flux in hepatocytes. Further detailed studies demonstrated that diclofenac induced a reactive oxygen species (ROS)-dependent increase in lysosomal pH, attenuated cathepsin activity and blocked autophagosome-lysosome fusion. The reactivation of lysosomal function by treatment with clioquinol or transfection with the transcription factor EB restored lysosomal pH and thus autophagic flux. The production of mitochondrial ROS is critical for this process since scavenging ROS reversed lysosomal dysfunction and activated autophagic flux. The compromised lysosomal activity induced by diclofenac also inhibited the fusion with and degradation of mitochondria by mitophagy. Diclofenac-induced cell death and hepatotoxicity were effectively protected by rapamycin. Thus, we demonstrated that diclofenac induces the intracellular ROS production and lysosomal dysfunction that lead to the suppression of autophagy. Impaired autophagy fails to maintain mitochondrial integrity and aggravates the cellular ROS burden, which leads to diclofenac-induced hepatotoxicity.
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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.