Evidence map›Paper›PMID 38245795›Full record

ArticleEuropean journal of medical research2024

Amifostine ameliorates bleomycin-induced murine pulmonary fibrosis via NAD

Feng Guo, Feng Xu, Shujuan Li, Yun Zhang, Dan Lv, Lin Zheng, Yongxiong Gan, Miao Zhou, Keyu Zhao, Shuling Xu and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of medical research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

14 citing papers in PubMed, 15 citations in OpenAlex.

  1. Advances in metabolic reprogramming of pulmonary fibrosis.Chinese medical journal pulmonary and critical care medicine · 2026
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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 3 institutions in 1 country.

Feng Guo *Department of Biochemistry, Health Science Center, Ningbo University, Ningbo, 315041, China.
Feng Xu *Central Laboratory of the Medical Research Center, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Shujuan LiDepartment of Biochemistry, Health Science Center, Ningbo University, Ningbo, 315041, China.
Yun ZhangDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo University, Ningbo, 315041, China.
Dan LvDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo University, Ningbo, 315041, China.
Lin ZhengDepartment of Laboratory Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Yongxiong GanDepartment of Emergency Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Miao ZhouDepartment of Biochemistry, Health Science Center, Ningbo University, Ningbo, 315041, China.
Keyu ZhaoDepartment of Dermatology, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Shuling XuDepartment of Dermatology, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Bin WuDepartment of Pulmonary and Critical Care Medicine, South China Hospital Affiliated to Shenzhen University, Shenzhen, China.
Zaichun Deng *Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo University, Ningbo, 315041, China. dengzaichun@nbu.edu.cn.
Panfeng Fu *Department of Biochemistry, Health Science Center, Ningbo University, Ningbo, 315041, China. fupanfeng@nbu.edu.cn.
Ningbo University · CNNingbo University Affiliated Hospital · CNShenzhen University · CN

Funding

Medical Health Science and Technology Project of Zhejiang Province 2021KY1046Medical Health Science and Technology Project of Zhejiang Province 2022KY1145Medical Health Science and Technology Project of Zhejiang Province 2022KY333Ningbo Nature Science 202003N4023Ningbo Nature Science 2021J243Ningbo Nature Science 2021J244PAN3315 Innovative Individual of Ningbo Government 2020B-31-G
6 · The paper itself

Abstract

backgroundIdiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by irreversible scarring of the lung parenchyma. Despite various interventions aimed at mitigating several different molecular aspects of the disease, only two drugs with limited clinical efficacy have so far been approved for IPF therapy.

objectiveWe investigated the therapeutic efficacy of amifostine, a detoxifying drug clinically used for radiation-caused cytotoxicity, in bleomycin-induced murine pulmonary fibrosis.

methodsC57BL6/J mice were intratracheally instilled with 3 U/kg of bleomycin. Three doses of amifostine (WR-2721, 200 mg/kg) were administered intraperitoneally on days 1, 3, and 5 after the bleomycin challenge. Bronchoalveolar lavage fluid (BALF) was collected on day 7 and day 21 for the assessment of lung inflammation, metabolites, and fibrotic injury. Human fibroblasts were treated in vitro with transforming growth factor beta 1 (TGF-β1), followed by amifostine (WR-1065, 1-4 µg/mL) treatment. The effects of TGF-β1 and amifostine on the mitochondrial production of reactive oxygen species (ROS) were assessed by live cell imaging of MitoSOX. Cellular metabolism was assessed by the extracellular acidification rate (ECAR), the oxygen consumption rate (OCR), and the concentrations of various energy-related metabolites as measured by mass spectrum (MS). Western blot analysis was performed to investigate the effect of amifostine on sirtuin 1 (SIRT1) and adenosine monophosphate activated kinase (AMPK).

resultsThree doses of amifostine significantly attenuated lung inflammation and pulmonary fibrosis. Pretreatment and post-treatment of human fibroblast cells with amifostine blocked TGF-β1-induced mitochondrial ROS production and mitochondrial dysfunction in human fibroblast cells. Further, treatment of fibroblasts with TGF-β1 shifted energy metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) and towards glycolysis, as observed by an altered metabolite profile including a decreased ratio of NAD + /NADH and increased lactate concentration. Treatment with amifostine significantly restored energy metabolism and activated SIRT1, which in turn activated AMPK. The activation of AMPK was required to mediate the effects of amifostine on mitochondrial homeostasis and pulmonary fibrosis. This study provides evidence that repurposing of the clinically used drug amifostine may have therapeutic applications for IPF treatment.

conclusionAmifostine inhibits bleomycin-induced pulmonary fibrosis by restoring mitochondrial function and cellular metabolism.

Indexed as

AmifostineIdiopathic Pulmonary FibrosisPneumoniaAMP-Activated Protein KinasesAnimalsBleomycinFibroblastsHumansLungMiceMice, Inbred C57BLMitochondriaNADReactive Oxygen SpeciesSirtuin 1Transforming Growth Factor beta1AmifostineAMP-Activated Protein KinasesBleomycinNADReactive Oxygen SpeciesSIRT1 protein, humanSirtuin 1Transforming Growth Factor beta1AmifostineIPFMetabolismMitochondriaNAD+ROSSIRT1TGF-β1

Identifiers

PMID38245795
PMCPMC10799491
OpenAlexW4391052474

What OpenQuestion holds

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LicenceCC BY
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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.