CO-releasing molecules (CO-RMs) are compounds that contains a heavy metal or iron surrounded by carbonyl (CO) group as coordinated ligands. They can produce the CO in the biological systems, which can be used to treat diseased tissues such as inflammatory diseases[1]. CORM-3 (tricarbonylchloro(glycinato)ruthenium(II)) is a synthesized water-soluble form of metal carbonyl that can release CO in physiological conditions. Raw 264.7 cells were treated with 10 μg/ml LPS and then incubated with 50 – 600 μM of CORM-3 for 24h. The amount of NO measured by the accumulation of nitrite was increased by LPS and attenuated by CORM-3 in a dose dependent manner. 48 hours after incubation of CORM-3, the production of IL-1beta measured by ELISA was diminished up to 61% at a concentration of 400 μM of CORM-3[2]. Rat H9c2 cardiac cells were incubated with 10, 25 or 50 μmol/L of CORM-3 under hypoxic conditions for 24 hours, the cell viability was recovered to 100% at 25 μmol/L of CORM-3 and above[3]. Male BALB/c mice were intraperitoneal administration of 40 mg/kg CORM-3 at 1 day and 15 minutes before cardiac harvest, and the hearts were transplanted into male CBA mice. One dose of CORM-3 was given to the recipients 1 day before surgery, 30 minutes before cardiac reperfusion, and 1 hour after transplantation. It was found that the survival rate of the mice treatement with CORM-3 was significantly higher than the control group[3].
作用机制
The biologically compatible ligand (glycine) was coordinated on the metal center of CORM-3, to promote the dissociation of the CO in biological environment[4].
CORM-3 细胞实验
Cell Line
Concentration
Treated Time
Description
References
H9c2 cells
50 μmol/L
1 hour
To evaluate H2O2-induced apoptosis and cell death, results showed that HO-1 TG myocytes were resistant to H2O2-induced cell death
Circulation. 2010 May 4;121(17):1912-25.
Escherichia coli K-12 strain MG1655
60 μM
1 hour
To evaluate the antimicrobial activity of CORM-3 against E. coli and its intracellular Ru accumulation. Results showed that CORM-3 significantly inhibited bacterial growth and increased intracellular Ru levels, directly correlating with cytotoxicity.
Redox Biol. 2018 Sep;18:114-123.
Cardiomyocytes
100 µM
30 minutes
To evaluate the effect of CORM-3 on mitochondrial membrane potential, results showed that CORM-3 pretreatment attenuated PAO-induced MPT
Circulation. 2010 May 4;121(17):1912-25.
Human colon carcinoma cell line RKO
25 μM
1 hour
To assess the cytotoxicity of CORM-3 on mammalian cells and its intracellular Ru accumulation. Results demonstrated that CORM-3 significantly reduced cell survival, correlating with intracellular Ru accumulation levels.
Redox Biol. 2018 Sep;18:114-123.
Primary neurons
100 μM
3 hours pretreatment
To evaluate the effect of CORM-3 on neurons under oxygen-glucose deprivation (OGD) conditions, results showed that CORM-3 inhibited OGD-induced IRE1 phosphorylation and inflammasome expression
EBioMedicine. 2019 Feb;40:643-654.
CORM-3 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
Spinal cord injury model
8 mg/kg
Not used
CORM-3 alleviates neuron death by inhibiting the activation of caspase-1 and caspase-11 and the release of pro-inflammatory factors IL-1β and IL-18
J Adv Res. 2020 Aug 18;28:97-109
Mice
Myocardial infarction model
Intraperitoneal injection
40 mg/kg
Once daily for 24 days
To evaluate the effect of CORM-3 on post-infarction LV remodeling, results showed that CORM-3 treatment attenuated LV dilatation and dysfunction
Circulation. 2010 May 4;121(17):1912-25.
Sprague-Dawley rats
Spinal cord injury model
Tail vein injection
8 mg/kg/day
Once daily until sacrifice
To evaluate the effect of CORM-3 on neuron death and motor functional recovery after spinal cord injury, results showed that CORM-3 alleviated neuron death and improved motor functional recovery
EBioMedicine. 2019 Feb;40:643-654.
C57BL/6J mice
Chronic ethanol-induced liver injury model
Intraperitoneal injection
3 mg/kg
Once daily for 5 days
To evaluate the therapeutic effect of CORM-A1 on ethanol-induced liver injury, it was found that CORM-A1 reduced ethanol-induced increases in AST and ALT, decreased expression of inflammatory cytokines TNF α, IL6 and CXCL10, and reduced accumulation of the hepatocyte death marker M30 and expression of RIP3.
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