EUK-134 is a synthetic superoxide dismutase and catalase mimetic. EUK-134 produced a significant reduction in renal dysfunction and injury caused by I/R(ischemia/reperfusion). EUK-134 significantly reduced renal injury caused by oxidative stress in vivo (reduction in PAR formation), and in vitro EUK-134 reduced PTC injury and death caused by H2O2. In vitro, EUK-134 significantly reduced NO (nitric oxide) production by PTCs (proximal tubular cell) incubated with IFN-gamma/LPS(lipopolysaccharide)[3]. Pretreatment with EUK-134 (10 μM) was effective in the prevention of hypertrophic changes in H9C2 cells, reduction of oxidative stress, and prevention of metabolic shift. EUK-134 treatment improved the oxidative status of mitochondria and reversed hypertrophy-induced reduction of mitochondrial membrane potential[4]. After a 75-min left renal artery clamping, a single intravenous injection of EUK-134 at 0.2 mg/kg, just before unclamping, provided significantly better renal function recovery during the week after the ischemic insult compared with recovery of untreated animals[5].In addition, the EUK-8 and EUK-134 improved NASH (Nonalcoholic steatohepatitis) athological features in liver of MCD(methionine/choline-deficient )-fed rats[6].
EUK-134 细胞实验
Cell Line
Concentration
Treated Time
Description
References
IB3-1 cells
50 μg ml–1
18 hours
EUK-134 enhanced the membrane stability of ΔF508-CFTR and maintained its function
Autophagy. 2012 Nov;8(11):1657-72.
CFBE41o- cells
50 μg ml–1
18 hours
EUK-134 stabilized ΔF508-CFTR at the plasma membrane and maintained its function
Autophagy. 2012 Nov;8(11):1657-72.
HUVECs
1 μM
2-hour pretreatment
EUK-134 pretreatment attenuated the H2O2-, Ang II-, and ox-LDL-induced SREBP2 and miR-92a levels
Circulation. 2015 Mar 3;131(9):805-14.
ΔCytochrome b 143B cells
10 μM
30 minutes or 60 minutes
EUK-134 inhibited the hypoxic activation of AMPK in ΔCytochrome b cells, indicating that ROS is the key signaling molecule for AMPK activation.
Free Radic Biol Med. 2009 May 15;46(10):1386-91.
Wild-type mouse embryonic fibroblasts (MEFs)
10 μM
30 minutes or 60 minutes
EUK-134 abolished the hypoxic activation of AMPK, indicating that hypoxic activation of AMPK is dependent on ROS.
Free Radic Biol Med. 2009 May 15;46(10):1386-91.
MLE-12 cells
20 μM
24 hours
EUK-134 completely blocked asbestos- and H2O2-induced mtDNA damage and apoptosis.
EUK-134 significantly inhibited TGFβ1-induced H2O2 generation and collagen synthesis
Antioxidants (Basel). 2020 Nov 13;9(11):1126.
Primary rat alveolar type II cells
20 μM
Prevented PM-induced decrease in Na,K-ATPase activity
Am J Respir Cell Mol Biol. 2006 Jun;34(6):670-6.
A549 cells
5 μM
24 hours
Prevented PM-induced decrease in Na,K-ATPase membrane protein abundance
Am J Respir Cell Mol Biol. 2006 Jun;34(6):670-6.
EUK-134 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
ΔF508-CFTR mutant mice
In vitro culture
50 μg/ml
18 hours
EUK-134 stabilized ΔF508-CFTR expression at the airway surface by restoring autophagy and reduced inflammatory markers
Autophagy. 2012 Nov;8(11):1657-72.
Mice
Inhalation co-exposure model
Intraperitoneal injection
10 mg/kg
Single injection, lasting until 24 hours post-exposure
EUK-134 significantly blunted lung inflammation and respiratory function decline confirming the role of oxidant imbalance.
Redox Biol. 2021 Oct;46:102092
Mice
Formalin-induced inflammatory pain model
Intraperitoneal injection
25 mg/kg
Single injection, observed for 1 hour
EUK-134 significantly reduced formalin-induced inflammatory pain responses, but the analgesic effects of EUK-134 and N2O were not additive. This suggests that reduced ROS levels led to decreased inflammation, but without the presence of ROS, N2O was not able to provide additional analgesia.
J Physiol. 2011 Jan 1;589(Pt 1):135-48
Mice (C57BL/6)
Radiation-induced pneumopathy model
Intraperitoneal injection
10 μg/g body weight
Three times a week for 3 weeks
To investigate the protective effect of EUK-134 on radiation-induced endothelial cell loss. Results showed that EUK-134 treatment restored the radiation-induced reduction of VE-Cad expression levels and reduced lung fibrosis development.
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