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Inhibition of desmoglein-1 by aspirin leads to synthetic lethality of keratinocytes in Shuanghuanglian-induced cutaneous eruption response.
- Source :
-
Toxicology letters [Toxicol Lett] 2021 Oct 01; Vol. 349, pp. 145-154. Date of Electronic Publication: 2021 Jun 11. - Publication Year :
- 2021
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Abstract
- Cutaneous eruptions caused by the combination of Chinese and Western medicine have attracted widespread attention; however, the underlying mechanism remains unclear. This study aimed to evaluate the potential mechanism of cutaneous eruptions in vivo and in vitro using the combination of Shuanghuanglian injection powder (SHL) and aspirin (ASA) as an example. ASA and SHL co-administration induced inflammatory responses in HaCat cells, as evidenced by marked increases in the expression of IL-4 and TNF-α, and the level of apoptosis. Additionally, histopathological investigation of mice skin tissues showed local inflammatory cell infiltration. Western boltting was used to detect the effects of ASA on desmoglein-1 (DSG1) expression; we found that DSG1 expression was down-regulated in vivo and in vitro. Finally, the key components of SHL were administered to HaCat cells with down-regulated DSG1; it was seen that neochlorogenic acid and rutin have a significant effect on HaCat cell apoptosis. These results demonstrate that DSG1 deficiency is a potential cause of cutaneous eruptions caused by the combination of SHL and ASA, and neochlorogenic acid and rutin are the main allergenic components. This study provides a new research strategy for the safety evaluation of integrated traditional Chinese and Western medicine.<br />Competing Interests: Declaration of Competing Interest The authors report no declarations of interest.<br /> (Copyright © 2021. Published by Elsevier B.V.)
- Subjects :
- Animals
Chlorogenic Acid analogs & derivatives
Chlorogenic Acid toxicity
Desmoglein 1 metabolism
Drug Eruptions metabolism
Drug Eruptions pathology
Female
HaCaT Cells
Humans
Inflammation Mediators metabolism
Interleukin-4 metabolism
Keratinocytes metabolism
Keratinocytes pathology
Mice, Inbred ICR
Quinic Acid analogs & derivatives
Quinic Acid toxicity
Rutin toxicity
Tumor Necrosis Factor-alpha metabolism
Mice
Apoptosis drug effects
Aspirin toxicity
Desmoglein 1 antagonists & inhibitors
Drug Eruptions etiology
Drugs, Chinese Herbal toxicity
Keratinocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 349
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 34126182
- Full Text :
- https://doi.org/10.1016/j.toxlet.2021.06.005