ArticleBiomedicines2023
Targeting Autophagy, Apoptosis, and Oxidative Perturbations with Dapagliflozin Mitigates Cadmium-Induced Cognitive Dysfunction in Rats.
Article in Biomedicines, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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
18 citing papers in PubMed, 26 citations in OpenAlex.
- Protective effect of dapagliflozin against phenytoin-induced cerebellar dysfunction and histological alterations in rats: the role of SIRT1/Nrf2/HO-1 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The impact of animal models on translating male infertility research from bench to bedside: a narrative review.Reproductive biology and endocrinology : RB&E · 2026Review
- Dapagliflozin ameliorates Alzheimer's disease in rats via stimulating the protective arm of renin angiotensin system and suppressing neuroinflammation.Inflammopharmacology · 2026Article
- Dapagliflozin attenuates hypothyroidism induced liver and lung dysfunction via regulation of mitophagy and apoptosis.Molecular biology reports · 2026Article
- Neuroprotective Potential of SGLT2 Inhibitors in Animal Models of Alzheimer's Disease and Type 2 Diabetes Mellitus: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The Potential Role of SGLT2 Inhibitors in the Treatment of Depression: Mechanisms and Clinical Prospects.Drug design, development and therapy · 2026Review
- ATG5-dependent autophagy in Sertoli cells protects against cadmium-disrupted blood-testis barrier via perturbing CXCL2/CXCR2 axis.Cell biology and toxicology · 2025Article
- The SGLT2 Inhibitor Dapagliflozin Disrupts the Cell Cycle at High Concentrations Without Altering Glycosphingolipid (De Novo)Biosynthesis.International journal of molecular sciences · 2025Article
- Dapagliflozin Ameliorates Doxorubicin-Induced Chemobrain and Cognitive Abnormalities in Rats: Modulation of AKT/GSK-3β and Wnt/β-Catenin Pathways.Neurochemical research · 2025Article
- Review
- Exploring Dapagliflozin's Influence on Autophagic Flux in Mania-like Behaviour: Insights from the LKB1/AMPK/LC3 Pathway in a Mouse Model.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Article
- Life-threatening risk factors contribute to the development of diseases with the highest mortality through the induction of regulated necrotic cell death.Cell death & disease · 2025Review
- Effect of Interaction of ATG7 and Plasma Metal Concentrations on Cognitive Impairment in Rural China.Journal of molecular neuroscience : MN · 2025Article
- Article
- Repurposing Dapagliflozin for Mitigation of the Kidney Injury Triggered by Cadmium in Rats: Role of Autophagy, Apoptosis, and the SIRT1/Nrf2/HO-1 Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Single and joint exposure of Pb, Cd, Hg, Se, Cu, and Zn were associated with cognitive function of older adults.Scientific reports · 2024Article
- Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
Abstract
Cognitive decline and Alzheimer-like neuropathology are common manifestations of cadmium toxicity. Thanks to its antioxidant/anti-apoptotic features, dapagliflozin has demonstrated promising neuroprotective actions. However, its effect on cadmium-induced neurotoxicity is lacking. The present work aimed to examine whether dapagliflozin could protect rats from cadmium-evoked cognitive decline. In this study, the behavioral disturbances and hippocampal biomolecular alterations were studied after receiving dapagliflozin. Herein, cadmium-induced memory/learning decline was rescued in the Morris water maze, novel object recognition task, and Y-shaped maze by dapagliflozin. Meanwhile, the hippocampal histopathological abnormalities were mitigated. The molecular mechanisms revealed that dapagliflozin lowered hippocampal expression of p-tau and Aβ42 neurotoxic proteins while augmenting acetylcholine. The cognitive enhancement was triggered by hippocampal autophagy stimulation, as indicated by decreased SQSTM-1/p62 and Beclin 1 upregulation. Meanwhile, a decrease in p-mTOR/total mTOR and an increase in p-AMPK/total AMPK ratio were observed in response to dapagliflozin, reflecting AMPK/mTOR cascade stimulation. Dapagliflozin, on the other hand, dampened the pro-apoptotic processes in the hippocampus by downregulating Bax, upregulating Bcl-2, and inactivating GSK-3β. The hippocampal oxidative insult was mitigated by dapagliflozin as seen by lipid peroxide lowering, antioxidants augmentation, and SIRT1/Nrf2/HO-1 pathway activation. In conclusion, dapagliflozin's promising neuroprotection was triggered by its pro-autophagic, anti-apoptotic, and antioxidant properties.
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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.