ArticleInternational journal of cardiology2016
Diclofenac induces proteasome and mitochondrial dysfunction in murine cardiomyocytes and hearts.
Article in International journal of cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Olaparib alleviates diclofenac-induced toxicity in HepG2 cells via modulation of oxidative stress and mitochondrial functions.Molecular and cellular biochemistry · 2026Article
- Biotransformation of common NSAIDs by Cunninghamella species and resulting metabolite toxicity.Scientific reports · 2026Article
- Stage-Dependent Embryolethality of Diclofenac Sodium: Quantitative Assessment of Dose-Time Interaction and Critical Windows of Susceptibility in the In Ovo Chicken Embryo Model.Veterinary sciences · 2026Article
- Montelukast attenuates diclofenac sodium-induced cardiotoxicity in male rats via targeting Wnt/β-catenin pathway.Scientific reports · 2026Article
- SIRT3 activation protects from nabumetone-induced mitochondrial toxicity in adult human cardiomyocytes.Cellular and molecular life sciences : CMLS · 2026Article
- Systemic administration of analgesic buprenorphine, but not carprofen, affects cardiomyocyte contractility in rodents.Journal of molecular and cellular cardiology plus · 2025Article
- Eicosanoids Signals in SARS-CoV-2 Infection: A Foe or Friend.Molecular biotechnology · 2024Review
- Diclofenac sensitizes multi-drug resistant Acinetobacter baumannii to colistin.PLoS pathogens · 2024Article
- Sequestosome 1 (p62) mitigates hypoxia-induced cardiac dysfunction by stabilizing hypoxia-inducible factor 1α and nuclear factor erythroid 2-related factor 2.Cardiovascular research · 2024Article
- Modeling drug-induced mitochondrial toxicity with human primary cardiomyocytes.Science China. Life sciences · 2024Article
- Article
- Mitochondrial HAntioxidants (Basel, Switzerland) · 2023Article
- Predicting molecular mechanism of silymarin-potentiated diclofenac toxicity: Insight fromToxicology reports · 2023Article
- Stress-mediated aggregation of disease-associated proteins in amyloid bodies.Scientific reports · 2023Article
- Platinum(IV) Derivatives of [Pt(1Journal of medicinal chemistry · 2023Article
- Neuroprotective effects of the PPARβ/δ antagonist GSK0660 in in vitro and in vivo Parkinson's disease models.Biological research · 2023Article
- Drug-induced mitochondrial toxicity: Risks of developing glucose handling impairments.Frontiers in endocrinology · 2023Review
- Development and Challenges of Diclofenac-Based Novel Therapeutics: Targeting Cancer and Complex Diseases.Cancers · 2022Review
- Assessing Drug-Induced Mitochondrial Toxicity in Cardiomyocytes: Implications for Preclinical Cardiac Safety Evaluation.Pharmaceutics · 2022Review
- Ibuprofen alters epoxide hydrolase activity and epoxy-oxylipin metabolites associated with different metabolic pathways in murine livers.Scientific reports · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundOne of the most common nonsteroidal anti-inflammatory drugs (NSAIDs) used worldwide, diclofenac (DIC), has been linked to increased risk of cardiovascular disease (CVD). The molecular mechanism(s) by which DIC causes CVD is unknown.
methodsProteasome activities were studied in hearts, livers, and kidneys from male Swiss Webster mice treated with either 100mg/kg DIC for 18h (acute treatment) or 10mg/kg DIC for 28days (chronic treatment). Cultured H9c2 cells and neonatal cardiomyocytes were also treated with different concentrations of DIC and proteasome function, cell death and ROS generation studied. Isolated mouse heart mitochondria were utilized to determine the effect of DIC on various electron transport chain complex activities.
resultsDIC significantly inhibited the chymotrypsin-like proteasome activity in rat cardiac H9c2 cells, murine neonatal cardiomyocytes, and mouse hearts, but did not affect proteasome subunit expression levels. Proteasome activity was also affected in liver and kidney tissues from DIC treated animals. The levels of polyubiquitinated proteins increased in hearts from DIC treated mice. Importantly, the levels of oxidized proteins increased while the β5i immunoproteasome activity decreased in hearts from DIC treated mice. DIC increased ROS production and cell death in H9c2 cells and neonatal cardiomyocytes while the cardioprotective NSAID, aspirin, had no effect on ROS levels or cell viability. DIC inhibited mitochondrial Complex III, a major source of ROS, and impaired mitochondrial membrane potential suggesting that mitochondria are the major sites of ROS generation.
conclusionThese results suggest that DIC induces cardiotoxicity by a ROS dependent mechanism involving mitochondrial and proteasome dysfunction.
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