Inhibiting hydrogen sulfide production in umbilical stem cells reduces their protective effects during experimental necrotizing enterocolitis.

Introduction: Umbilical mesenchymal stem cells (USC) have been shown to reduce illness in animal models of necrotizing enterocolitis (NEC), possibly through the paracrine release of hydrogen sulfide (HS). We hypothesized that animals treated with USCs with inhibited HS synthesis would exhibit more severe disease.

Methods: NEC was induced in five-day-old mouse pups by formula feeding and hypoxic and hypothermic stress.

Interleukin-6 Therapy Improves Intestinal Recovery Following Ischemia.

Background: Interleukin-6 (IL6) has both proinflammatory and anti-inflammatory pathways, but its effects on intestinal recovery following ischemia are unknown. We hypothesized that administration of IL6 following intestinal ischemia would improve mesenteric perfusion and mucosal injury.

Methods: Adult male C57Bl6J mice were anesthetized, and a laparotomy was performed.

Hydrogen Sulfide Donor GYY4137 Acts Through Endothelial Nitric Oxide to Protect Intestine in Murine Models of Necrotizing Enterocolitis and Intestinal Ischemia.

Background: Necrotizing enterocolitis (NEC) in premature infants is often a devastating surgical condition with poor outcomes. GYY4137 is a long-acting donor of hydrogen sulfide, a gasotransmitter that is protective against intestinal injury in experimental NEC, likely through protection against injury secondary to ischemia. We hypothesized that administration of GYY4137 would improve mesenteric perfusion, reduce intestinal injury, and reduce inflammatory responses in experimental NEC and ischemia-reperfusion injury, and that these benefits would be mediated through endothelial nitric oxide synthase-dependent pathways.

The route and timing of hydrogen sulfide therapy critically impacts intestinal recovery following ischemia and reperfusion injury.

Purpose: Hydrogen sulfide (HS) has many beneficial properties and may serve as a novel treatment in patients suffering from intestinal ischemia-reperfusion injury (I/R). The purpose of this study was to examine the method of delivery and timing of administration of HS for intestinal therapy during ischemic injury. We hypothesized that 1) route of administration of hydrogen sulfide would impact intestinal recovery following acute mesenteric ischemia and 2) preischemic HS conditioning using the optimal mode of administration as determined above would provide superior protection compared to postischemic application.

Loss of endothelial nitric oxide synthase exacerbates intestinal and lung injury in experimental necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) continues to be a devastating condition among preterm infants. Nitric oxide, which is synthesized in the intestine by endothelial nitric oxide synthase (eNOS), acts as a potent vasodilator and antioxidant within the mesentery and may play a role in prevention of NEC. We hypothesized that loss of endothelial nitric oxide would worsen both intestinal and associated lung injury and increase local and systemic inflammation during experimental NEC.