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Neuroprotective Impact of Linagliptin against Cadmium-Induced Cognitive Impairment and Neuropathological Aberrations: Targeting SIRT1/Nrf2 Axis, Apoptosis, and Autophagy
Arab HH, Eid AH, Alsufyani SE, Ashour AM, El-Sheikh AAK, Darwish HW, Georgy GS.. Pharmaceuticals (Basel, Switzerland), 2023-07-27
Topic: Brain proteins, microglia and lab models
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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APA 7th
Arab, H. H., Eid, A. H., Alsufyani, S. E., Ashour, A. M., El-Sheikh, A. A. K., Darwish, H. W., et al. (2023). Neuroprotective Impact of Linagliptin against Cadmium-Induced Cognitive Impairment and Neuropathological Aberrations: Targeting SIRT1/Nrf2 Axis, Apoptosis, and Autophagy. Pharmaceuticals (Basel, Switzerland). https://doi.org/10.3390/ph16081065
Vancouver
Arab HH, Eid AH, Alsufyani SE, Ashour AM, El-Sheikh AAK, Darwish HW, et al. Neuroprotective Impact of Linagliptin against Cadmium-Induced Cognitive Impairment and Neuropathological Aberrations: Targeting SIRT1/Nrf2 Axis, Apoptosis, and Autophagy. Pharmaceuticals (Basel, Switzerland). 2023. doi:10.3390/ph16081065. PMID: 37630980.
BibTeX
@article{arab2023-37630980,
author = {Arab, H. H. and Eid, A. H. and Alsufyani, S. E. and Ashour, A. M. and El-Sheikh, A. A. K. and Darwish, H. W. and Georgy, G. S.},
title = {{Neuroprotective Impact of Linagliptin against Cadmium-Induced Cognitive Impairment and Neuropathological Aberrations: Targeting SIRT1/Nrf2 Axis, Apoptosis, and Autophagy}},
journal = {Pharmaceuticals (Basel, Switzerland)},
year = {2023},
doi = {10.3390/ph16081065},
pmid = {37630980},
url = {https://doi.org/10.3390/ph16081065}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- 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.
- 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.
- The behavioral recovery was associated with dampening of the hippocampal pro-oxidant response alongside SIRT1/Nrf2/HO-1 axis stimulation.
- In conclusion, linagliptin's antioxidant, antiapoptotic, and pro-autophagic properties advocated its promising neuroprotective impact.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Pharmaceuticals (Basel, Switzerland)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37630980) |
| Free to read | 2 / 2 | Free to read |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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