ArticleBiological trace element research2026
Disruption of the SIRT1/PI3K/AKT Signaling Axis Mediates Fluoride-Induced Cardiotoxicity: Evidence from in Vitro and Zebrafish Models.
Article in Biological trace element research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Chasing the FoxO in Metabolic Disorders: Novel Considerations for Oxidative Stress, Programmed Cell Death, Wnt, and the Gut Microbiome.Antioxidants (Basel, Switzerland) · 2026Review
- Dementia, mood disorders, and aging: Bridging new avenues of care through shared biological pathways.Aging advancesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
Fluoride (F), an environmental contaminant, is known to induce cardiotoxicity, although the precise molecular mechanisms remain unclear. This study aimed to investigate the role of the SIRT1/PI3K/AKT signaling pathway in F-induced cardiotoxicity and explore the potential protective effects of SIRT1 activation. Human AC16 cardiomyocytes and zebrafish embryos were exposed to increasing concentrations of sodium NaF. Cellular assays were used to assess viability, apoptosis, cell cycle distribution, and oxidative stress. Expression levels of oxidative and inflammatory markers, as well as components of the SIRT1/PI3K/AKT pathway, were analyzed by western blotting, immunofluorescence, and real-time PCR. Zebrafish were evaluated for cardiac developmental abnormalities, apoptosis, and oxidative stress. The SIRT1 agonist SRT1720 was used to evaluate the protective effects of SIRT1 activation. Statistical analysis was performed using SPSS 23 Software and GraphPad Prism7 software, with significant differences evaluated by one-way analysis of variance (ANOVA) and Dunnett's test (p < 0.05). NaF exposure significantly inhibited AC16 cell proliferation, induced G1 phase arrest, and increased apoptosis in a dose-dependent manner. Reactive oxygen species levels were elevated, accompanied by downregulation of antioxidant proteins and upregulation of inflammatory cytokines. NaF markedly suppressed SIRT1, PI3K, and AKT expression while activating FOXO1a. Zebrafish embryos exhibited dose-dependent cardiac malformations, increased apoptosis, and elevated oxidative stress markers. Treatment with SRT1720 restored SIRT1/PI3K/AKT pathway activity, enhanced cell proliferation, reduced apoptosis, and alleviated oxidative and inflammatory responses in both cell and zebrafish models. This study demonstrates that F induces cardiotoxicity by disrupting the SIRT1/PI3K/AKT signaling pathway, leading to increased oxidative stress, inflammation, and apoptosis. Activation of SIRT1 by SRT1720 mitigates these effects, highlighting the protective role of this pathway in F-related cardiac injury. These findings provide mechanistic insights and identify potential molecular targets for the prevention and treatment of fluorosis-associated cardiovascular toxicity.
Indexed as
Identifiers
What OpenQuestion holds
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.