Evidence map›Paper›PMID 42128922›Full record

ArticleArchives of toxicology2026

Rosiglitazone hepatotoxicity resulting from hepatic protein covalent binding derived from its aldehyde metabolite.

Yanjia Zhao, Yi Yang, Zifang Ding, Yao Sun, Mingyu Zhang, Weiwei Li, Ting Liu, Zixia Hu, Ying Peng, Jiang Zheng

Abstract read
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In one paragraph

Article in Archives of toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Yanjia ZhaoWuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, Liaoning, People's Republic of China.
Yi YangWuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, Liaoning, People's Republic of China.
Zifang DingWuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, Liaoning, People's Republic of China.
Yao SunWuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, Liaoning, People's Republic of China.
Mingyu ZhangWuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, Liaoning, People's Republic of China.
Weiwei LiState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Guizhou Medical University, Guiyang, 550004, People's Republic of China.
Ting LiuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Guizhou Medical University, Guiyang, 550004, People's Republic of China.
Zixia HuSchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, People's Republic of China. huzixia@syphu.edu.cn.
Ying PengWuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, Liaoning, People's Republic of China. yingpeng1999@163.com.
Jiang ZhengWuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, Liaoning, People's Republic of China. zhengjiang@syphu.edu.cn.ORCID 0000-0002-8187-2147

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rosiglitazone (RGZ), a thiazolidinedione insulin sensitizer, is widely used in the treatment of type 2 diabetes mellitus. However, concerns regarding its dose-dependent hepatotoxicity have emerged, and the mechanisms of the toxic action remain elusive. This study aimed to investigate the mechanism by which an aldehyde metabolite generated through metabolic activation of RGZ forms covalent adduction with protein lysine residues and its contribution to hepatotoxicity. Using in vitro liver microsomal incubations coupled with LC-MS/MS, the reactive aldehyde metabolite and its corresponding lysine adduct were identified. It was verified that RGZ was primarily metabolized by CYP3A and CYP2E1 into an electrophilic aldehyde metabolite which subsequently underwent covalent bonding with the ε-amino group of lysine residues. The formation of the protein adduction was found to be associated with the hepatotoxicity of RGZ.

Indexed as

AldehydesChemical and Drug Induced Liver InjuryHypoglycemic AgentsLiverThiazolidinedionesActivation, MetabolicAnimalsCytochrome P-450 CYP2E1Cytochrome P-450 CYP3AHumansLysineMaleMicrosomes, LiverPPAR-gamma AgonistsProtein BindingRosiglitazoneAldehydesCytochrome P-450 CYP2E1Cytochrome P-450 CYP3AHypoglycemic AgentsLysinePPAR-gamma AgonistsRosiglitazoneThiazolidinedionesHepatotoxicityMetabolic activationProtein adductionRosiglitazone

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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.