ArticleMedical science monitor : international medical journal of experimental and clinical research2017
Klotho Improves Cardiac Function by Suppressing Reactive Oxygen Species (ROS) Mediated Apoptosis by Modulating Mapks/Nrf2 Signaling in Doxorubicin-Induced Cardiotoxicity.
Article in Medical science monitor : international medical journal of experimental and clinical research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Soluble Klotho, a biomarker and therapeutic strategy to reduce bronchopulmonary dysplasia and pulmonary hypertension in preterm infants.Scientific reports · 2020Trial
- Serum α-Klotho and SIRT1 - Relationship with graft function, inflammation and hospitalization rates in kidney transplant recipients.Transplant international : official journal of the European Society for Organ Transplantation · 2026Observational
- The aging choroid plexus and its relationship with gut dysbiosis and Klotho decline: possible intervention strategies.GeroScience · 2025Review
- Klotho alleviates oxidative stress and mitochondrial dysfunction through the Nrf2/HO-1 pathway, thereby reducing renal senescence induced by calcium oxalate crystals.Urolithiasis · 2025Article
- Klotho enhances stability of chronic kidney disease atherosclerotic plaques by inhibiting GRK2/PLC-β-mediated endoplasmic reticulum stress in macrophages via modulation of the ROS/SHP1 pathway.Scientific reports · 2024Article
- Long-Term Pentoxifylline Therapy Is Associated with a Reduced Risk of Atherosclerotic Cardiovascular Disease by Inhibiting Oxidative Stress and Cell Apoptosis in Diabetic Kidney Disease Patients.Antioxidants (Basel, Switzerland) · 2024Article
- Review
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- Early aging and premature vascular aging in chronic kidney disease.Clinical kidney journal · 2023Review
- Decreased Klotho Expression Causes Accelerated Decline of Male Fecundity through Oxidative Injury in Murine Testis.Antioxidants (Basel, Switzerland) · 2023Article
- Nrf2: a dark horse in doxorubicin-induced cardiotoxicity.Cell death discovery · 2023Review
- Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice.Nutrients · 2023Article
- Klotho, Oxidative Stress, and Mitochondrial Damage in Kidney Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Coenzyme Q10 protects against doxorubicin-induced cardiomyopathy via antioxidant and anti-apoptotic pathway.Tissue barriers · 2023Article
- Synergistic impacts of Montelukast and Klotho against doxorubicin-induced cardiac toxicity in Rats.Toxicology research · 2022Article
- Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations.Frontiers in aging · 2022Review
- Renal Function Mediates the Association Between Klotho and Congestive Heart Failure Among Middle-Aged and Older Individuals.Frontiers in cardiovascular medicine · 2022Article
- The Potential of Gamma Secretase as a Therapeutic Target for Cardiac Diseases.Journal of personalized medicine · 2021Review
- Klotho overexpression suppresses apoptosis by regulating the Hsp70/Akt/Bad pathway in H9c2(2-1) cells.Experimental and therapeutic medicine · 2021Article
- The Emerging Key Role of Klotho in the Hypothalamus-Pituitary-Ovarian Axis.Reproductive sciences (Thousand Oaks, Calif.) · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND Anthracyclines-induced cardiotoxicity has become one of the major restrictions of their clinical applications. Klotho showed cardioprotective effects. This study aimed to investigate the effects and possible mechanisms of klotho on doxorubicin (DOX)-induced cardiotoxicity. MATERIAL AND METHODS Rats and isolated myocytes were exposed to DOX and treated with exogenous klotho. Specific inhibitors and siRNAs silencing MAPKs were also used to treat the animals and/or myocytes. An invasive hemodynamic method was used to determine cardiac functions. Intracellular ROS generation was evaluated by DHE staining. Western blotting was used to determine the phosphorylation levels of JNK, ERK, and p38 MAPKs in plasma extracts and Nrf2 in nuclear extracts. Nuclear translocation of Nrf2 in myocytes was evaluated by immunohistochemistry. Cell apoptosis was evaluated by TUNEL assay and flow cytometry. RESULTS Klotho treatment improved DOX-induced cardiac dysfunction in rats. The DOX-induced ROS accumulation and cardiac apoptosis were attenuated by klotho. Impaired phosphorylations of MAPKs, Nrf2 translocation and expression levels of HO1 and Prx1 were also attenuated by klotho treatment. However, the anti-oxidant and anti-apoptotic effects of klotho on DOX-exposed myocardium and myocytes were impaired by both specific inhibitors and siRNAs against MAPKs. Moreover, the recovery effects of klotho on phosphorylations of MAPKs, Nrf2 translocation and expression levels of HO1 and Prx1 were also impaired by specific inhibitors and siRNAs against MAPKs. CONCLUSIONS By recovering the activation of MAPKs signaling, klotho improved cardiac function loss which was triggered by DOX-induced ROS mediated cardiac apoptosis.
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Registered trials
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.