Anticancer Drug 2-Methoxyestradiol Protects against Renal IschemiaReperfusion Injury by Reducing Inflammatory Cytokines Expression
Joint Authors
So, Edmund Cheung
Yeh, Ching-Hua
Chen, Ying-Yin
Wang, Li-Yun
Sun, Ding-Ping
Hsing, Chung-Hsi
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-08-25
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Background.
Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure and allograft dysfunction in kidney transplantation.
ROS/inflammatory cytokines are involved in I/R injury.
2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, inhibits inflammatory cytokine expression and is an antiangiogenic and antitumor agent.
We investigated the inhibitory effect of 2ME2 on renal I/R injury and possible molecular actions.
Methods.
BALB/c mice were intraperitoneally injected with 2ME2 (10 or 20 mg/kg) or vehicle 12 h before and immediately after renal I/R experiments.
The kidney weight, renal function, tubular damages, and apoptotic response were examined 24 h after I/R injury.
The expression of mRNA of interleukin-1β, tumor necrosis factor- (TNF) α, caspase-3, hypoxia inducible factor- (HIF) 1α, and proapoptotic Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) in kidney tissue was determined using RT-PCR, while the expression of nuclear factor κB (NF-κB), BCL-2, and BCL-xL, activated caspase-9, and HIF-1α was determined using immunoblotting.
In vitro, we determined the effect of 2ME2 on reactive oxygen species (ROS) production and cell viability in antimycin-A-treated renal mesangial (RMC) and tubular (NRK52E) cells.
Results.
Serum creatinine and blood urea nitrogen were significantly higher in mice with renal I/R injury than in sham control and in I/R+2ME2-treated mice.
Survival in I/R+2ME2-treated mice was higher than in I/R mice.
Histological examination showed that 2ME2 attenuated tubular damage in I/R mice, which was associated with lower expression TNF-α, IL-1β, caspase-9, HIF-1α, and BNIP3 mRNA in kidney tissue.
Western blotting showed that 2ME2 treatment substantially decreased the expression of activated caspase-9, NF-κB, and HIF-1α but increased the antiapoptotic proteins BCL-2 and BCL-xL in kidney of I/R injury.
In vitro, 2MR2 decreased ROS production and increased cell viability in antimycin-A-treated RMC and NRK52E cells.
Conclusions.
2ME2 reduces renal I/R injury in mice because it inhibits the expression of ROS and proinflammatory cytokines and induces antiapoptotic proteins.
American Psychological Association (APA)
Chen, Ying-Yin& Yeh, Ching-Hua& So, Edmund Cheung& Sun, Ding-Ping& Wang, Li-Yun& Hsing, Chung-Hsi. 2014. Anticancer Drug 2-Methoxyestradiol Protects against Renal IschemiaReperfusion Injury by Reducing Inflammatory Cytokines Expression. BioMed Research International،Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-471752
Modern Language Association (MLA)
Chen, Ying-Yin…[et al.]. Anticancer Drug 2-Methoxyestradiol Protects against Renal IschemiaReperfusion Injury by Reducing Inflammatory Cytokines Expression. BioMed Research International No. 2014 (2014), pp.1-11.
https://search.emarefa.net/detail/BIM-471752
American Medical Association (AMA)
Chen, Ying-Yin& Yeh, Ching-Hua& So, Edmund Cheung& Sun, Ding-Ping& Wang, Li-Yun& Hsing, Chung-Hsi. Anticancer Drug 2-Methoxyestradiol Protects against Renal IschemiaReperfusion Injury by Reducing Inflammatory Cytokines Expression. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-471752
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-471752