Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh.
Naunyn Schmiedebergs Arch Pharmacol. 2011 Jul;384(1):93-102. doi: 10.1007/s00210-011-0653-7. Epub 2011 May 17.
Wound microenvironment presents widespread oxidant stress, inflammation, and onslaught of apoptosis. Carbon monoxide (CO) exerts pleiotropic cellular effects by modulating intracellular signaling pathways which translate into cellular protection against oxidative stress, inflammation, and apoptosis. CO-releasing molecules (CO-RMs) deliver CO in a controlled manner without altering carboxyhemoglobin levels. This study observed a potential therapeutic value of CO in the wound healing by using tricarbonyldichlororuthenium (II) dimer (CO-releasing molecule (CO-RM)-2), as one of the novel CO-releasing agent. The effect of CO-RM-2 treatment was studied on wound contraction, glucosamine, hydroxyproline levels, and mRNA of cytokines/adhesion molecule in rats using a full-thickness cutaneous wound model and angiogenesis in chick chorioallantoic membrane (CAM) model. CO-RM-2 treatment increased cellular proliferation and collagen synthesis as evidenced by the increase in wound contraction and hydroxyproline and glucosamine contents. The mRNA expression of cytokines endorsed fast healing, as was indicated by the inhibition of pro-inflammatory adhesion molecules such as ICAM-1 and cytokine TNF-α and upregulation of anti-inflammatory cytokine IL-10. An ELISA assay of IL-10 and TNF-α cytokines revealed pro-healing modulation in excision wound by CO-RM-2 treatment. CO-RM significantly promoted the angiogenesis as compared to the iCO-RM group in vitro in CAM model demonstrating pro-angiogenic effects of CO-RM-2 in wound healing process. These results indicate that CO-RM-2 may have a potential application in the management of recalcitrant/obstinate wounds wherein, active wound healing is desired. This study also opens up a new area of research for the synthesis of novel CO-releasing molecules to be used for such purposes.
伤口微环境呈现广泛的氧化剂应激、炎症和细胞凋亡。一氧化碳 (CO) 通过调节细胞内信号通路发挥多种细胞效应，从而使细胞免受氧化应激、炎症和凋亡的影响。一氧化碳释放分子 (CO-RM) 以可控的方式释放 CO，而不会改变碳氧血红蛋白水平。本研究通过使用三羰基二氯钌 (II) 二聚体 (CO 释放分子 (CO-RM)-2) 作为新型 CO 释放剂之一，观察了 CO 在伤口愈合中的潜在治疗价值。使用全层皮肤伤口模型和鸡胚绒毛尿囊膜 (CAM) 模型研究了 CO-RM-2 处理对大鼠伤口收缩、葡萄糖胺、羟脯氨酸水平和细胞因子/粘附分子 mRNA 的影响。CO-RM-2 处理增加了细胞增殖和胶原合成，这表现为伤口收缩和羟脯氨酸和葡萄糖胺含量增加。细胞因子的 mRNA 表达支持快速愈合，因为促炎粘附分子如 ICAM-1 和细胞因子 TNF-α 的抑制和抗炎细胞因子 IL-10 的上调表明了这一点。IL-10 和 TNF-α 细胞因子的 ELISA 检测显示 CO-RM-2 处理的切除伤口有促愈合调节作用。与 iCO-RM 组相比，CO-RM 在体外 CAM 模型中显著促进了血管生成，这表明 CO-RM-2 在伤口愈合过程中有促血管生成作用。这些结果表明，CO-RM-2 可能在需要积极伤口愈合的顽固性/顽固伤口的治疗中具有潜在的应用。本研究还为合成用于此类目的的新型 CO 释放分子开辟了一个新的研究领域。
