CORM 2

CORM 2 is a carbon monoxide-releasing molecule that can liberate a controlled amount of CO in biological systems and has been developed as a carbon monoxide donor^[1-2]. When CORM 2 is in contact with reduced deoxymyoglobin or deoxyhaemoglobin rapidly transfers ca. one CO equivalent to the protein haem, forming carboxymyoglobin (COMb) or carboxyhaemoglobin (COHb), respectively^[3]. In addition, CORM 2 also exerts a protective effect against gastric mucosal injury induced by 75% ethanol^[4].

In vitro, after treating human umbilical vein endothelial cells (HUVECs) with 100µM CORM 2 for 0-5min, a bidirectional current can be recorded. This current is insensitive to the small-, intermediate-, and large-conductance Ca²⁺-activated K⁺ channel blockers apamin (the small-conductance Ca²⁺-activated K⁺ channel blocker), TRAM-34 (the intermediate-conductance Ca²⁺-activated K⁺ channel blocker), and iberiotoxin (the big-conductance Ca²⁺-activated K⁺ channel blocker), and it is not affected by EGTA in the pipette solution^[2]. RAW264.7 murine macrophage cell line was exposed to P. intermedia lipopolysaccharide (LPS) (10μg/mL) together with escalating concentrations of CORM 2 (12.5, 25, 50, 100μM) for 24h (NO) or 48h (IL-1β), and the release of both NO and IL-1β was markedly and dose-dependently suppressed^[5].

In vivo, intravenous infusion of CORM 2 at 10mg/kg/h for 30min (total 5mg/kg) after cardiac arrest significantly increased neurological deficit scores (NDS), reduced S-100B levels, and improved 3-day survival in resuscitated Sprague-Dawley rats^[6]. Administering CORM 2 (30mg/kg; i.p.) before a lethal dose of LPS significantly attenuated the severe hypothermia induced by LPS in C57BL/6 mice^[7].

References:
[1] Khir NAM, Noh ASM, Long I, et al. Recent progress on anti-nociceptive effects of carbon monoxide releasing molecule-2 (CORM-2). Mol Cell Biochem. 2024;479(3):539-552.
[2] Dong DL, Chen C, Huang W, et al. Tricarbonyldichlororuthenium (II) dimer (CORM2) activates non-selective cation current in human endothelial cells independently of carbon monoxide releasing. Eur J Pharmacol. 2008;590(1-3):99-104.
[3] Fagone P, Mangano K, Coco M, et al. Therapeutic potential of carbon monoxide in multiple sclerosis. Clin Exp Immunol. 2012;167(2):179-187.
[4] Magierowska K, Magierowski M, Hubalewska-Mazgaj M, et al. Carbon Monoxide (CO) Released from Tricarbonyldichlororuthenium (II) Dimer (CORM-2) in Gastroprotection against Experimental Ethanol-Induced Gastric Damage. PLoS One. 2015;10(10):e0140493.
[5] Choi EY, Keum BR, Choe SH, et al. Tricarbonyldichlororuthenium(II) dimer, the lipid-soluble carbon monoxide-releasing molecule, attenuates Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1β in murine macrophages. Int Immunopharmacol. 2021;90:107190.
[6] Wang P, Yao L, Zhou LL, et al. Carbon Monoxide Improves Neurologic Outcomes by Mitochondrial Biogenesis after Global Cerebral Ischemia Induced by Cardiac Arrest in Rats. Int J Biol Sci. 2016;12(8):1000-1009.
[7] Riquelme SA, Bueno SM, Kalergis AM. Carbon monoxide down-modulates Toll-like receptor 4/MD2 expression on innate immune cells and reduces endotoxic shock susceptibility. Immunology. 2015;144(2):321-332

CORM 2是一种能在生物体系中可控释放一氧化碳的CO释放分子，已被开发用作一氧化碳供体^[1-2]。当CORM 2与还原态脱氧肌红蛋白或脱氧血红蛋白接触时，可迅速向蛋白血红素转移约1当量的CO，分别形成碳氧肌红蛋白（COMb）或碳氧血红蛋白（COHb）^[3]。此外，CORM 2还对75%乙醇诱发的胃黏膜损伤具有保护作用^[4]。

在体外，用100µM的CORM 2处理人脐静脉内皮细胞（HUVECs）0-5min后即可记录到双向电流。这一电流不受小电导（apamin）、中电导（TRAM-34）和大电导（iberiotoxin）钙激活钾通道阻断剂的影响，也不受电极液中EGTA的干扰^[2]。RAW264.7小鼠巨噬细胞在含10µg/mL的P. intermedia脂多糖（LPS）的培养液中加入递增浓度的CORM 2（12.5、25、50、100µM），分别作用24h（测NO）或48h（测IL-1β），结果显示NO和IL-1β的释放均呈剂量依赖性显著降低^[5]。

在体内，心脏骤停后给Sprague-Dawley大鼠静脉输注10mg/kg/h的CORM 2持续30min（总量5mg/kg），可显著提高神经功能缺损评分（NDS）、降低S-100B水平，并改善复苏后3天生存率^[6]。在致死剂量LPS攻击前给予C57BL/6小鼠腹腔注射30mg/kg的CORM 2，可显著减轻LPS诱导的严重低体温^[7]。