ArticleScientific reports2020
Activated ROCK/Akt/eNOS and ET-1/ERK pathways in 5-fluorouracil-induced cardiotoxicity: modulation by simvastatin.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- Multifactorial mechanisms of 5-fluorouracil-induced cardiotoxicity and the cardioprotective role of gallic acid.Molecular biology reports · 2026Article
- A Comprehensive Overview on Chemotherapy-Induced Cardiotoxicity: Insights into the Underlying Inflammatory and Oxidative Mechanisms.Cardiovascular drugs and therapy · 2025Review
- HIF1A regulates follicular atresia through O-GlcNAcylation-mediated VEZF1/ET-1/FOXO1/BAX signaling in porcine granulosa cells.Journal of animal science and biotechnology · 2025Article
- Expression differences and relationships of endothelin-1, interleukin-6 and c-kit in hypertensive patients with and without depression.World journal of psychiatry · 2025Article
- Pathological Investigation of the Effect of Bovine Colostrum Against 5-FU-Induced Liver, Kidney, and Heart Toxicity in Rats.Life (Basel, Switzerland) · 2025Article
- Cancer-Therapy-Related Cardiac Dysfunction: Latest Advances in Prevention and Treatment.Life (Basel, Switzerland) · 2025Review
- Taxifolin Protects Against 5-Fluorouracil-Induced Cardiotoxicity in Mice Through Mitigating Oxidative Stress, Inflammation, and Apoptosis: Possible Involvement of Sirt1/Nrf2/HO-1 Signaling.Cardiovascular toxicology · 2025Article
- Ameliorative Effect of N-Acetylcysteine Against 5-Fluorouracil-Induced Cardiotoxicity via Targeting TLR4/NF-κB and Nrf2/HO-1 Pathways.Medicina (Kaunas, Lithuania) · 2025Article
- NO/NOS system dysregulation as a key molecular mechanism in chemotherapy-induced cardiotoxicity: a review.Frontiers in cardiovascular medicine · 2025Review
- Exercise pre-conditioning prevents vascular toxicity caused by infusion of 5-fluorouracil in male rats.American journal of cancer research · 2025Article
- Interrelation of Natural Polyphenol and Fibrosis in Diabetic Nephropathy.Molecules (Basel, Switzerland) · 2024Review
- Ameliorative effect of Melatonin on 5-Fluorouracil-induced reproductive toxicity in male rats.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Article
- Statins in Mitigating Anticancer Treatment-Related Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms, Clinical Management and Innovative Treatment.Drug design, development and therapy · 2024Review
- Molecular mechanism of empagliflozin cardioprotection in 5-fluorouracil (5-FU)-induced cardiotoxicity via modulation of SGLT2 and TNFα/TLR/NF-κB signaling pathway in rats.Toxicological research · 2024Article
- Endothelin receptor antagonists (ERAs) can potentially be used as therapeutic drugs to reduce hypertension caused by small molecule tyrosine kinase inhibitors (TKIs).Frontiers in pharmacology · 2024Review
- Impaired microvascular reactivity in patients treated with 5-fluorouracil chemotherapy regimens: Potential role of endothelial dysfunction.International journal of cardiology. Heart & vasculature · 2023Article
- Interactions between Angiotensin Type-1 Antagonists, Statins, and ROCK Inhibitors in a Rat Model of L-DOPA-Induced Dyskinesia.Antioxidants (Basel, Switzerland) · 2023Article
- An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.Cellular & molecular biology letters · 2023Review
- Statins Show Anti-Atherosclerotic Effects by Improving Endothelial Cell Function in a Kawasaki Disease-like Vasculitis Mouse Model.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Fluorouracil (5-FU) is used in the treatment of different solid tumors; however, its use is associated with rare, but serious cardiotoxicity. Nevertheless, the involvement of ROCK/NF-κB, Akt/eNOS and ET-1/ERK1/2 trajectories in the cardiotoxic effect and in the potential cardioprotective upshot of simvastatin has been elusive. Male Wistar rats were allocated into 5-FU (50 mg/kg/week; i.p, 6 weeks), simvastatin (15 mg/kg/day; p.o, 8 weeks) treated groups and simvastatin + 5-FU, besides the normal control group. 5-FU-induced cardiotoxicity boosted the serum level of N-terminal pro-brain (B-type) natriuretic peptide (NT-proBNP), aortic contents of endothelin (ET)-1 and thromboxane (TX) A2, as well as cardiac contents of NADPH oxidases (Nox), cyclooxygenase (COX)-2, malondialdehyde (MDA), phosphorylated Akt (p-Akt), phosphorylated extracellular signal-regulated kinase (p-ERK)1/2 and the protein expressions of rho-kinase (ROCK) and caspase-3. On the other hand, it suppressed cardiac reduced glutathione (GSH) and phosphorylated endothelial nitric oxide synthase (p-eNOS). Contrariwise, co-administration with simvastatin overcame these disturbed events and modulated the ROCK/NF-κB, Akt/eNOS and ET-1/ERK1/2 signaling pathways. This study highlights other mechanisms than coronary artery spasm in the 5-FU cardiotoxicity and reveals that NT-proBNP is a potential early marker in this case. Moreover, the cross-talk between ROCK/ NF-κB, ROS/COX-2/TXA2, Akt/eNOS and ET-1/ERK1/2 pathways contributes via different means to upsetting the vasoconstriction/vasodilatation equilibrium as well as endothelial cell function and finally leads to cardiomyocyte stress and death-the modulation of these trajectories offers simvastatin its potential cardio-protection against 5-FU.
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