Evidence mapPaperPMID 29095437Full record

ArticleCell death & disease2017

Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I.

Sunbin Ling, Qiaonan Shan, Peng Liu, Tingting Feng, Xuanyu Zhang, Penghui Xiang, Kangchen Chen, Haiyang Xie, Penghong Song, Lin Zhou and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
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

29 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025
    Review
  7. Article
  8. Review
  9. The regulatory roles and clinical significance of glycolysis in tumor.Cancer communications (London, England) · 2024
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
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

13 authors at 4 institutions in 3 countries.

Sunbin LingDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Qiaonan ShanDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Peng LiuDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Tingting FengDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xuanyu ZhangDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Penghui XiangDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Kangchen ChenDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Haiyang XieKey Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
Penghong SongKey Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
Lin ZhouKey Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
Jimin LiuDepartment of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Shusen ZhengDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xiao XuDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Blood Center of Zhejiang Province · CNFirst Affiliated Hospital Zhejiang University · CNZhejiang University · CNMcMaster University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Arsenic trioxide (ATO) is a well-accepted chemotherapy agent in managing promyelocytic leukemia. ATO often causes severe health hazards such as hepatotoxicity, dermatosis, neurotoxicity, nephrotoxicity and cardiotoxicity. The production of reactive oxygen species, (ROS) play a significant role in ATO-induced hepatotoxicity. The oral hypoglycemic drug, metformin, is considered to be a potential novel agent for chemoprevention in the treatment of cancer. Moreover, metformin has also been shown to have hepatoprotective effects. In the present study, we demonstrated that metformin protected normal hepatocytes from ATO-induced apoptotic cell death in vitro and in vivo. Gene expression screening revealed that glucose metabolism might be related to the metformin-induced protective effect on ATO-treated AML12 cells. The metformin-promoted or induced glycolysis was not responsible for the protection of AML12 cells from ATO-induced apoptotic cell death. Instead, metformin increased the intracellular NADH/NAD+ ratio by inhibiting mitochondrial respiratory chain complex I, further decreasing the intracellular ROS induced by ATO. Treatment with low glucose or rotenone, a mitochondrial respiratory chain complex I inhibitor, also protected AML12 cells from ATO-induced apoptotic cell death. We show for the first time that metformin protects the hepatocyte from ATO by regulating the mitochondrial function. With its properties of chemoprevention, chemosensitization and the amelioration of liver damage, metformin has great prospects for clinical application other than type 2 diabetes mellitus (T2DM).

Indexed as

AnimalsAntineoplastic AgentsApoptosisArsenicalsArsenic TrioxideCell LineChemical and Drug Induced Liver InjuryElectron Transport Complex IGlucoseGlycolysisHumansLeukemia, MyeloidMaleMetforminMiceNADAntineoplastic AgentsArsenicalsArsenic TrioxideElectron Transport Complex IGlucoseMetforminNADOxidesReactive Oxygen SpeciesRotenone

Identifiers

PMID29095437
PMCPMC5775401
OpenAlexW2765429845

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.