Metal-based carbon monoxide (CO)-releasing molecules have been shown to exert anti-inflammatory and anti-oxidative properties maintaining gastric mucosal integrity. We are interested in further development of metal-free CO-based therapeutics for oral administration. Thus, we examine the protective effect of representative CO prodrug, BW-CO-111, in rat models of gastric damage induced by necrotic ethanol or aspirin, a representative non-steroidal anti-inflammatory drug. Treatment effectiveness was assessed by measuring the microscopic/macroscopic gastric damage area and gastric blood flow by laser flowmetry. Gastric mucosal mRNA and/or protein expressions of HMOX1, HMOX2, nuclear factor erythroid 2-related factor 2, COX1, COX2, iNos, Anxa1 and serum contents of TGFB1, TGFB2, IL1B, IL2, IL4, IL5, IL6, IL10, IL12, tumor necrosis factor α, interferon γ, and GM-CSF were determined. CO content in gastric mucosa was assessed by gas chromatography. Pretreatment with BW-CO-111 (0.1 mg/kg, i.g.) increased gastric mucosal content of CO and reduced gastric lesions area in both models followed by increased GBF. These protective effects of the CO prodrug were supported by changes in expressions of molecular biomarkers. However, because the pathomechanisms of gastric damage differ between topical administration of ethanol and aspirin, the possible protective and anti-inflammatory mechanisms of BW-CO-111 may be somewhat different in these models.

金属基一氧化碳（CO）释放分子已显示出维持胃黏膜完整性的抗炎和抗氧化特性。我们对进一步开发用于口服给药的无金属基于CO的治疗剂感兴趣。因此，我们检查了代表性的CO前药BW-CO-111在由坏死性乙醇或阿司匹林（一种代表性的非甾体类抗炎药）诱发的胃损伤大鼠模型中的保护作用。通过用激光流量计测量微观/宏观胃损伤面积和胃血流量来评估治疗效果。胃黏膜mRNA和/或HMOX1，HMOX2，核因子红系2相关因子2，COX1，COX2，iNos，Anxa1的蛋白表达测定血清中TGFB1，TGFB2，IL1B，IL2，IL4，IL5，IL6，IL10，IL12，肿瘤坏死因子α，干扰素γ和GM-CSF的含量。通过气相色谱法评估胃粘膜中的CO含量。在两种模型中，BW-CO-111（0.1 mg / kg，ig）预处理均会增加胃粘膜中CO的含量并减少胃部病变区域，然后增加GBF。分子生物标记物表达的变化支持了CO前药的这些保护作用。但是，由于局部使用乙醇和阿司匹林之间胃损伤的发病机理不同，因此在这些模型中，BW-CO-111的可能的保护和抗炎机制可能有所不同。