Please use this identifier to cite or link to this item: https://doi.org/10.3390/ijms21031084
Title: Celastrol alleviates gamma irradiation-induced damage by modulating diverse inflammatory mediators
Authors: Wang, H. 
Ahn, K.S. 
Alharbi, S.A.
Shair, O.H.M.
Arfuso, F.
Sethi, G. 
Chinnathambi, A.
Tang, F.R. 
Keywords: Celastrol
Gamma radiation
In vitro
In vivo
NF??B
ROS
Issue Date: 2020
Publisher: MDPI AG
Citation: Wang, H., Ahn, K.S., Alharbi, S.A., Shair, O.H.M., Arfuso, F., Sethi, G., Chinnathambi, A., Tang, F.R. (2020). Celastrol alleviates gamma irradiation-induced damage by modulating diverse inflammatory mediators. International Journal of Molecular Sciences 21 (3) : 1084. ScholarBank@NUS Repository. https://doi.org/10.3390/ijms21031084
Rights: Attribution 4.0 International
Abstract: The present study aimed to explore the possible radioprotective effects of celastrol and relevant molecular mechanisms in an in vitro cell and in vivo mouse models exposed to gamma radiation. Human keratinocytes (HaCaT) and foreskin fibroblast (BJ) cells were exposed to gamma radiation of 20Gy, followed by treatment with celastrol for 24 h. Cell viability, reactive oxygen species (ROS), nitric oxide (NO) and glutathione (GSH) production, lipid peroxidation, DNA damage, inflammatory cytokine levels, and NF??B pathway activation were examined. The survival rate, levels of interleukin?6 (IL?6) and tumor necrosis factor alpha (TNF??) in blood, and p65 and phospho?p65 expression were also evaluated in mice after exposure to gamma radiation and celastrol treatment. The gamma irradiation of HaCaT cells induced decreased cell viability, but treatment with celastrol significantly blocked this cytotoxicity. Gamma irradiation also increased free radical production (e.g., ROS and NO), decreased the level of GSH, and enhanced oxidative DNA damage and lipid peroxidation in cells, which were effectively reversed by celastrol treatment. Moreover, inflammatory responses induced by gamma irradiation, as demonstrated by increased levels of IL?6, TNF??, and IL?1?, were also blocked by celastrol. The increased activity of NF??B DNA binding following gamma radiation was significantly attenuated after celastrol treatment. In the irradiated mice, treatment with celastrol significantly improved overall survival rate, reduced the excessive inflammatory responses, and decreased NF??B activity. As a NF??B pathway blocker and antioxidant, celastrol may represent a promising pharmacological agent with protective effects against gamma irradiation?induced injury. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Source Title: International Journal of Molecular Sciences
URI: https://scholarbank.nus.edu.sg/handle/10635/199044
ISSN: 1661-6596
DOI: 10.3390/ijms21031084
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_3390_ijms21031084.pdf2.57 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

14
checked on Dec 2, 2022

Page view(s)

116
checked on Dec 1, 2022

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons