Therapeutic roles of carbon monoxide in intestinal ischemia‐reperfusion injury

Abstract

Intestinal ischemia-reperfusion (I-R) injury is a complex, multifactorial, pathophysiological process with high morbidity and mortality, leading to serious difficulty in treatment. The mechanisms involved in the pathogenesis of intestinal I-R injury have been examined in detail and various therapeutic approaches for intestinal I-R injury have been developed; however, existing circumstances have not yet led to a dramatic change of treatment. Carbon monoxide (CO), one of the by-products of heme degradation by heme oxygenase (HO), is considered as a candidate for treatment of intestinal I-R injury and indeed HO-1-derived endogenous CO and exogenous CO play a pivotal role in protecting the gastrointestinal tract from intestinal I-R injury. Interestingly, anti-inflammatory effects of CO have been elucidated sufficiently in various cell types including endothelial cells, circulating leukocytes, macrophages, lymphocytes, epithelial cells, fibroblast, organ-specific cells, and immune-presenting cells. In this review, we herein focus on the therapeutic roles of CO in intestinal I-R injury and the cell-specific anti-inflammatory effects of CO, clearly demonstrating future therapeutic strategies of CO for treating intestine I-R injury.

CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression

“…Carbon monoxide (CO) is endogenously produced in cells and tissues as the byproduct of heme oxygenase (HO) enzymes after heme catalytic activity [13] , [14] . Although CO is toxic to human bodies at high concentration, low-dose exogenous CO (approximately 250–500 ppm) treatment has been demonstrated to have protective functions, anti-inflammatory and antiapoptotic effects in various human diseases [15] , [16] , [17] , [18] . Furthermore, accumulating studies over the past decade have shown that low concentration of CO, or CO-releasing molecules (CORMs), can confer several molecular mechanisms, including eliminating microbes, regulating cell death and organ dysfunction, and promote immune response through resolving mediator-heme oxygenase-1 circuits [19] , activation of p38 MAPK, enhanced PPAR-γ singaling, and suppression of TLRs translocation [13] , [16] , [20] .…”

Hydrogen: A Novel Option in Human Disease Treatment

“…In another study, the inhalation of 2% H 2 also attenuated intestinal injuries caused by severe sepsis in male Nrf2 KO mice by regulating HO-1 and HMGB1 release [ 122 ]. Moreover, an in vivo study revealed that H 2 inhalation improved the prognosis in patients with stage IV colorectal cancer by activating PGC-1 α and restoring exhausted CD8+ T cells [ 123 ].…”

“…Many animal models have established the efficacy of hydrogen against cancers. The attributes of hydrogen include blocking of the regulator for chromosome condensation [ 43 ], some crucial molecules in stemness [ 165 ], proliferation [ 123 ], and angiogenesis [ 165 ], and the alleviation of oxidative stress. The combination therapy of hydrogen and other novel antineoplastic drugs, such as LY294002 [ 166 ], which is an inhibitor of PI3K, has demonstrated great potential and efficacy.…”

“…Akagi [ 37 ] treated 55 stage IV colorectal carcinoma patients using hydrogen inhalation and documented enhanced mitochondrial activity due to the activation of PGC-1 α to reduce the proportion of terminal PD-1+ CD8+ T cells. The depletion of these cells is associated with improved cancer prognosis [ 37 , 123 ]. This therapeutic effect has also been confirmed in another trial conducted in one patient with metastatic gallbladder cancer [ 167 ].…”

Carbon Monoxide Attenuates Lipopolysaccharides (LPS)-Induced Acute Lung Injury in Neonatal Rats via Downregulation of Cx43 to Reduce Necroptosis

“…Recently, many studies demonstrated that CO, a by-product of heme catabolism, possesses various physiological effects including anti-inflammatory, anti-apoptotic, antioxidant, and anti-proliferative property in vitro and in vivo [26,27]. Therefore, CO was applied to treat organ stress including acute myocardial injury, acute spinal cord injury [28], acute kidney injury [29], and ALI [30].…”