Perioperative hydrogen gas inhalation significantly ameliorates intestinal transplant injury by reducing oxidative stress, suppressing inflammatory mediators, and preserving mucosal barrier function and smooth muscle contractility. The treatment also prevents remote lung inflammation, suggesting hydrogen inhalation represents a potent and clinically applicable therapeutic strategy for mitigating ischemia/reperfusion injury in intestinal transplantation.
Plain-Language Summary
This study tested whether breathing hydrogen gas could reduce damage to transplanted small intestines in rats. When intestines are transplanted, they experience a period without blood flow (ischemia) followed by blood flow restoration (reperfusion), which causes injury through oxidative stress (cellular damage from harmful molecules). Rats that breathed hydrogen gas showed better intestinal function, less inflammation, reduced cellular damage markers, and better preservation of the intestinal lining compared to rats breathing regular air.
Abstract
Ischemia/reperfusion (I/R) injury during small intestinal transplantation (SITx) frequently causes complications including dysmotility, inflammation and organ failure. Recent evidence indicates hydrogen inhalation eliminates toxic hydroxyl radicals. Syngeneic, orthotopic SITx was performed in Lewis rats with 3 h of cold ischemic time. Both donor and recipient received perioperative air or 2% hydrogen inhalation. SITx caused a delay in gastrointestinal transit and decreased jejunal circular muscle contractile activity 24 h after surgery. Hydrogen treatment resulted in significantly improved gastrointestinal transit, as well as jejunal smooth muscle contractility in response to bethanechol. The transplant induced upregulation in the inflammatory mediators CCL2, IL-1 beta, IL-6 and TNF-alpha were mitigated by hydrogen. Hydrogen significantly diminished lipid peroxidation compared to elevated tissue malondialdehyde levels in air-treated grafts demonstrating an antioxidant effect. Histopathological mucosal erosion and increased gut permeability indicated a breakdown in posttransplant mucosal barrier function which was significantly attenuated by hydrogen treatment. In recipient lung, hydrogen treatment also resulted in a significant abatement in inflammatory mRNA induction and reduced neutrophil recruitment. Hydrogen inhalation significantly ameliorates intestinal transplant injury and prevents remote organ inflammation via its antioxidant effects. Administration of perioperative hydrogen gas may be a potent and clinically applicable therapeutic strategy for intestinal I/R injury.
