Evidence map›Paper›PMID 38789868›Full record

ArticleCell biology and toxicology2024

Rutin attenuates ensartinib-induced hepatotoxicity by non-transcriptional regulation of TXNIP.

Wentong Wu, Jinjin Li, Yiming Yin, Yourong Zhou, Xiangliang Huang, Yashi Cao, Xueqin Chen, Yunfang Zhou, Jiangxia Du, Zhifei Xu and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell biology and toxicology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. 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

16 authors.

Wentong Wu *Center for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China.
Jinjin Li *Center for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China.
Yiming YinCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China.
Yourong ZhouCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China.
Xiangliang HuangCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China.
Yashi CaoCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China.
Xueqin ChenDepartment of Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou, 310002, China.
Yunfang ZhouThe Laboratory of Clinical Pharmacy, the Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, 323020, China.
Jiangxia DuCenter for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310017, China.
Zhifei XuCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China.
Bo YangInstitute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Qiaojun HeCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China.
Xiaochun YangCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China.
Yuhuai HuInnovation Institute of Hangzhou Yuhong Pharmatech Co.,LTD, Hangzhou, 310018, China.
Hao YanCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China. yh925@zju.edu.cn.
Peihua LuoCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Zhejiang, 310058, Hangzhou, China. peihualuo@zju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ensartinib, an approved ALK inhibitor, is used as a first-line therapy for advanced ALK-positive non-small cell lung cancer in China. However, the hepatotoxicity of ensartinib seriously limits its clinical application and the regulatory mechanism is still elusive. Here, through transcriptome analysis we found that transcriptional activation of TXNIP was the main cause of ensartinib-induced liver dysfunction. A high TXNIP level and abnormal TXNIP translocation severely impaired hepatic function via mitochondrial dysfunction and hepatocyte apoptosis, and TXNIP deficiency attenuated hepatocyte apoptosis under ensartinib treatment. The increase in TXNIP induced by ensartinib is related to AKT inhibition and is mediated by MondoA. Through screening potential TXNIP inhibitors, we found that the natural polyphenolic flavonoid rutin, unlike most reported TXNIP inhibitors can inhibit TXNIP by binding to TXNIP and partially promoting its proteasomal degradation. Further studies showed rutin can attenuate the hepatotoxicity of ensartinib without antagonizing its antitumor effects. Accordingly, we suggest that TXNIP is the key cause of ensartinib-induced hepatotoxicity and rutin is a potential clinically safe and feasible therapeutic strategy for TXNIP intervention.

Indexed as

ApoptosisCarrier ProteinsRutinAnimalsChemical and Drug Induced Liver InjuryHepatocytesHumansLiverMaleMiceMice, Inbred C57BLThioredoxinsCarrier ProteinsRutinThioredoxinsTXNIP protein, humanTxnip protein, mouseApoptosisEnsartinibHepatotoxicityRutinTXNIP

Identifiers

PMID38789868
PMCPMC11126486

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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.