Prolonged intestinal cold storage causes considerable mucosal breakdown, which could bolster bacterial translocation and cause life-threatening infection for the transplant recipient. The intestine has an intraluminal compartment, which could be a target for intervention, but has not yet been fully investigated. Hydrogen gas exerts organ protection and has used been recently in several clinical and basic research studies on topics including intestinal transplantation. In this study, we aimed to investigate the cytoprotective efficacy of intraluminally administered hydrogen-rich saline on cold IR injury in intestinal transplantation. Isogeneic intestinal transplantation with 6 hours of cold ischemia was performed on Lewis rats. Hydrogen-rich saline (H 2 concentration at 5 ppm) or normal saline was intraluminally introduced immediately before preservation. Graft intestine was excised 3 hours after reperfusion and analyzed. Histopathological analysis of control grafts revealed blunting of the villi and erosion. These mucosal changes were notably attenuated by intraluminal hydrogen. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h post-reperfusion. However, this decline in permeability was critically prevented by hydrogen treatment. IR-induced upregulation of proinflammatory cytokine mRNAs such as IL-6 was mitigated by hydrogen treatment. Western blot revealed that hydrogen treatment regulated loss of the transmembrane protein ZO-1. Hydrogen-rich saline intraluminally administered in the graft intestine modulated IR injury to transplanted intestine in rats. Successful abrogation of intestinal IR injury with a novel strategy using intraluminal hydrogen may be easily clinically applicable and will compellingly improve patient care after transplantation.

Background Acute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory properties, we hypothesized that daily repeated inhalation of hydrogen gas could suppress persistent lung inflammation by inducing functional changes in macrophages, and consequently inhibit lung fibrosis during late-phase lung injury. Methods To test this hypothesis, lung injury was induced in mice by intratracheal administration of bleomycin (1.0 mg/kg). Mice were exposed to control gas (air) or hydrogen (3.2% in air) for 6 h every day for 7 or 21 days. Respiratory physiology, tissue pathology, markers of inflammation, and macrophage phenotypes were examined. Results Mice with bleomycin-induced lung injury that received daily hydrogen therapy for 21 days (BH group) exhibited higher static compliance (0.056 mL/cmH2O, 95% CI 0.047–0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH2O, 95% CI 0.031–0.053, p = 0.02) and lower static elastance (BH 18.8 cmH2O/mL, [95% CI 15.4–22.2] vs. BA 26.7 cmH2O/mL [95% CI 19.6–33.8], p = 0.02). When the mRNA levels of pro-inflammatory cytokines were examined 7 days after bleomycin administration, interleukin (IL)-6, IL-4 and IL-13 were significantly lower in the BH group than in the BA group. There were significantly fewer M2-biased macrophages in the alveolar interstitium of the BH group than in the BA group (3.1% [95% CI 1.6–4.5%] vs. 1.1% [95% CI 0.3–1.8%], p = 0.008). Conclusions The results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury.

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et al, which published ahead of print on December 27, 2021, on page 10, line 4, the sentence reads incorrectly as:An apparent limitation of this study was to use a much higher concentration of CORM-3 (100 μmol/L) compared with previously published studies in which micromolar concentrations of this compound were used; however, we must emphasize that our approach consisted of treating the intestinal grafts ex vivo, not in vivo, thus providing the important information that metal carbonyls can be used to treat tissues and organs at much higher concentrations than previously thought.The correct statement is:The concentration of CORM-3 used in our current study (100 μM) was comparable to previously published works; however, we must emphasize that our approach consisted of treating the intestinal grafts ex vivo, not in vivo, thus providing the important information that metal carbonyls could be used to treat tissues and organs at much higher concentrations than previously thought. As the appropriate concentration is still unknown, future experiments to determine the minimal and most effective doses of CORM-3 in this setting will be required. REFERENCEObara T, Yamamoto H, Aokage T, et al. Luminal administration of a water-soluble carbon monoxide-releasing molecule (CORM-3) mitigates ischemia/reperfusion injury in rats following intestinal transplantation Transplantation.

Bile pigments, such as bilirubin and biliverdin, are end products of the heme degradation pathway in mammals and are widely known for their cytotoxic effects. However, recent studies have revealed that they exert cytoprotective effects through antioxidative, anti-inflammatory, and immunosuppressive properties. All these mechanisms are indispensable in the treatment of diseases in the field of emergency and critical care medicine, such as coronary ischemia, stroke, encephalomyelitis, acute lung injury/acute respiratory distress syndrome, mesenteric ischemia, and sepsis. While further research is required before the safe application of bile pigments in the clinical setting, their underlying mechanisms shed light on their utilization as therapeutic agents in the field of emergency and critical care medicine. This article aims to summarize the current understanding of bile pigments and re-evaluate their therapeutic potential in the diseases listed above.