The endoplasmic reticulum participated in drug metabolic toxicity

Covalent binding of reactive metabolites formed by drug metabolic activation with biological macromolecules is considered to be an important mechanism of drug metabolic toxicity. Recent studies indicate that the endoplasmic reticulum (ER) could play an important role in drug toxicity by participatin...

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Bibliographic Details
Published in:Cell biology and toxicology 2022-12, Vol.38 (6), p.945-961
Main Authors: Huang, Qingcai, Chen, Youwen, Zhang, Zhengjia, Xue, Zeyu, Hua, Zhenglai, Luo, Xinyi, Li, Yang, Lu, Cheng, Lu, Aiping, Liu, Yuanyan
Format: Article
Language:English
Subjects:
Apoptosis
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell death
Drug dosages
Drug-Related Side Effects and Adverse Reactions - metabolism
Endoplasmic reticulum
Endoplasmic Reticulum - metabolism
Endoplasmic Reticulum Stress
Enzymes
Humans
Inflammation
Life Sciences
Macromolecules
Metabolic activation
Metabolic rate
Metabolism
Metabolites
Pharmacology/Toxicology
Protein folding
Proteins
Review
Toxicity
Unfolded Protein Response
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Summary:Covalent binding of reactive metabolites formed by drug metabolic activation with biological macromolecules is considered to be an important mechanism of drug metabolic toxicity. Recent studies indicate that the endoplasmic reticulum (ER) could play an important role in drug toxicity by participating in the metabolic activation of drugs and could be a primarily attacked target by reactive metabolites. In this article, we summarize the generation and mechanism of reactive metabolites in ER stress and their associated cell death and inflammatory cascade, as well as the systematic modulation of unfolded protein response (UPR)-mediated adaptive pathways. Graphical abstract
ISSN:0742-2091
1573-6822
DOI:10.1007/s10565-021-09689-8