ArticlePharmaceuticals (Basel, Switzerland)2023
Neuroprotective Impact of Linagliptin against Cadmium-Induced Cognitive Impairment and Neuropathological Aberrations: Targeting SIRT1/Nrf2 Axis, Apoptosis, and Autophagy.
Article in Pharmaceuticals (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Neurotoxic mechanisms of cadmium in neurodegenerative diseases.Frontiers in cell and developmental biology · 2026Review
- The SGLT2i "canagliflozin" and the DPP-4i "sitagliptin" mitigate hypertensive nephropathy in adult male rats by modulating the Ang II/RAGE/Nox4/NLRP3 cascade.Frontiers in physiology · 2026Article
- Therapeutic potential of porphyran in mitigating ischemia-reperfusion injury in gerbil hippocampus.Histology and histopathology · 2026Article
- Protective Role of Linagliptin in Cisplatin-Mediated Liver Injury: Involvement of STAT3 and AMPK/SIRT1/PGC-1alpha Mitochondrial Energy Sensing Networks.Advances in pharmacological and pharmaceutical sciences · 2026Article
- More Than Three Decades After Discovery of the Neuroprotective Effect of PACAP, What Is Still Preventing Its Clinical Use?Journal of molecular neuroscience : MN · 2025Review
- Unlocking the Neuroprotective Effect of Quercetin Against Cadmium-Induced Hippocampal Damage in Rats: PPARγ Activation as a Key Mechanism.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Gastroprotective Effect of Linagliptin on Indomethacin-Induced Gastric Ulceration in Mice: Crosstalk Between Oxidative Stress and Inflammasome Pathways.ACS pharmacology & translational science · 2025Article
- Study on the mechanism of activating SIRT1/Nrf2/p62 pathway to mediate autophagy-dependent ferroptosis to promote healing of diabetic foot ulcers.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Effect of Interaction of ATG7 and Plasma Metal Concentrations on Cognitive Impairment in Rural China.Journal of molecular neuroscience : MN · 2025Article
- Unlocking the potential of GLP-1 receptor agonists in ocular therapeutics: from molecular pathways to clinical impact.Frontiers in pharmacology · 2025Review
- Activation of AMPK/mTOR-Driven Autophagy and Suppression of the HMGB1/TLR4 Pathway with Pentoxifylline Attenuates Doxorubicin-Induced Hepatic Injury in Rats.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2/HO-1 and HIF-1α/CTGF/PAI-1.Molecular biology reports · 2024Article
- Sirtuins as Players in the Signal Transduction ofInternational journal of molecular sciences · 2024Review
- Mechanisms of Cadmium Neurotoxicity.International journal of molecular sciences · 2023Review
- Targeting Autophagy, Apoptosis, and Oxidative Perturbations with Dapagliflozin Mitigates Cadmium-Induced Cognitive Dysfunction in Rats.Biomedicines · 2023Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
Abstract
Cadmium is an environmental contaminant associated with marked neurotoxicity and cognitive impairment. Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has demonstrated promising neuroprotection against cerebral ischemia and diabetic dementia. However, there has been no study of its effect on cadmium-induced cognitive deficits. In the present work, linagliptin's prospective neuroprotective effects against cadmium-evoked cognitive decline were examined in vivo in rats. The molecular pathways related to oxidative stress, apoptosis, and autophagy were investigated. Histology, immunohistochemistry, ELISA, and biochemical assays were performed on brain hippocampi after receiving linagliptin (5 mg/kg/day). The current findings revealed that cadmium-induced learning and memory impairment were improved by linagliptin as seen in the Morris water maze, Y-maze, and novel object recognition test. Moreover, linagliptin lowered hippocampal neurodegeneration as seen in histopathology. At the molecular level, linagliptin curtailed hippocampal DPP-4 and augmented GLP-1 levels, triggering dampening of the hippocampal neurotoxic signals Aβ42 and p-tau in rats. Meanwhile, it enhanced hippocampal acetylcholine and GABA and diminished the glutamate spike. The behavioral recovery was associated with dampening of the hippocampal pro-oxidant response alongside SIRT1/Nrf2/HO-1 axis stimulation. Meanwhile, linagliptin counteracted hippocampal apoptosis markers and inhibited the pro-apoptotic kinase GSK-3β. In tandem, linagliptin activated hippocampal autophagy by lowering SQSTM-1/p62 accumulation, upregulating Beclin 1, and stimulating AMPK/mTOR pathway. In conclusion, linagliptin's antioxidant, antiapoptotic, and pro-autophagic properties advocated its promising neuroprotective impact. Thus, linagliptin may serve as a management approach against cadmium-induced cognitive deficits.
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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.