Evidence map›Paper›PMID 38956251›Full record

ArticleScientific reports2024

Disulfiram downregulates ferredoxin 1 to maintain copper homeostasis and inhibit inflammation in cerebral ischemia/reperfusion injury.

Shuai Yang, Xudong Li, Jinhong Yan, Fangchao Jiang, Xuehui Fan, Jing Jin, Weihua Zhang, Di Zhong, Guozhong Li

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. From copper imbalance to immunometabolic remodeling: cuproptosis-related vulnerability and therapeutic hypotheses in autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Copper Homeostasis and Cuproptosis in Neurological Disorders.Drug design, development and therapy · 2026
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025
    Review
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Shuai YangThe First Afliated Hospital of Harbin Medical University, 23 You Zheng Street, Harbin, 150001, China.
Xudong LiThe Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Harbin, 150001, China.
Jinhong YanThe Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Harbin, 150001, China.
Fangchao JiangThe First Afliated Hospital of Harbin Medical University, 23 You Zheng Street, Harbin, 150001, China.
Xuehui FanThe First Afliated Hospital of Harbin Medical University, 23 You Zheng Street, Harbin, 150001, China.
Jing JinHeilongjiang Provincial Hospital, Harbin, China.
Weihua ZhangThe First Afliated Hospital of Harbin Medical University, 23 You Zheng Street, Harbin, 150001, China.
Di ZhongThe First Afliated Hospital of Harbin Medical University, 23 You Zheng Street, Harbin, 150001, China. dityan@163.com.
Guozhong LiThe First Afliated Hospital of Harbin Medical University, 23 You Zheng Street, Harbin, 150001, China. lgzhyd1962@163.com.

Funding

Heilongjiang Province Key R&D Program Grant No. JD22C002
6 · The paper itself

Abstract

In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion (CI-RI) injury by modulating ferredoxin 1 (FDX1) to regulate copper ion (Cu) levels and inhibiting inflammatory responses. To simulate CI-RI, a transient middle cerebral artery occlusion (tMCAO) model in C57/BL6 mice was employed. Mice were administered with or without DSF before and after tMCAO. Changes in infarct volume after tMCAO were observed using TTC staining. Nissl staining and hematoxylin-eosin (he) staining were used to observe the morphological changes of nerve cells at the microscopic level. The inhibitory effect of DSF on initial inflammation was verified by TUNEL assay, apoptosis-related protein detection and iron concentration detection. FDX1 is the main regulatory protein of copper death, and the occurrence of copper death will lead to the increase of HSP70 stress and inflammatory response. Cuproptosis-related proteins and downstream inflammatory factors were detected by western blotting, immunofluorescence staining, and immunohistochemistry. The content of copper ions was detected using a specific kit, while electron microscopy was employed to examine mitochondrial changes. We found that DSF reduced the cerebral infarction volume, regulated the expression of cuproptosis-related proteins, and modulated copper content through down regulation of FDX1 expression. Moreover, DSF inhibited the HSP70/TLR-4/NLRP3 signaling pathway. Collectively, DSF could regulate Cu homeostasis by inhibiting FDX1, acting on the HSP70/TLR4/NLRP3 pathway to alleviate CI/RI. Accordingly, DSF could mitigate inflammatory responses and safeguard mitochondrial integrity, yielding novel therapeutic targets and mechanisms for the clinical management of ischemia-reperfusion injury.

Indexed as

CopperDisulfiramHomeostasisInflammationMice, Inbred C57BLReperfusion InjuryAnimalsApoptosisBrain IschemiaDisease Models, AnimalDown-RegulationInfarction, Middle Cerebral ArteryIron-Sulfur ProteinsMaleMiceMitochondriaCopperDisulfiramIron-Sulfur ProteinsNeuroprotective AgentsToll-Like Receptor 4

Identifiers

PMID38956251
PMCPMC11219760

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Registered trials

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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.