Glutathione.

Glutathione (GSH) is an ubiquitous thiol-containing tripeptide that plays a key role in cell biology. It modulates cell response to redox changes associated with the reactive oxygen species, detoxifies the metabolites of drugs; regulates gene expression and apoptosis, and is involved in the transmembrane transport of organic solutes. Polymorphism has been observed in key enzymes of GSH metabolism and some alleles have been associated with an impaired redox buffer system downsteam diseases, and susceptibility to ischaemia. These varied activities make GSH an attractive target for a more reductionist approach to the prevention and management of many conditions of interest to surgeons.

The role of glutathione in intestinal dysfunction.

Glutathione plays an important cytoprotective role in the gut. Animal studies have demonstrated that the provisions of glutathione precursors are protective for different types of free-radical-mediated cellular injury. There is a need to clarify the potential role of glutathione supplementation in ischemia-reperfusion injury and inflammatory bowel disease. More speculative is whether treatment with glutathione precursors can modify the progress of colorectal cancer.

Influence of glycine on intestinal ischemia-reperfusion injury.

BACKGROUND: It has been reported that glycine may protect donor small intestine against hypothermic ischemia before transplantation. This is consistent with the documented role of glycine as a natural cytoprotectant. OBJECTIVE: Using an in vivo rodent model, we sought to determine whether exposure to a 20% glycine solution reduces the extent of warm ischemia-reperfusion injury. METHODS: Wistar rats (n = 50) underwent laparotomy. A baseline group did not receive any further intervention. The remaining animals had cannulation of the aorta before the initiation of intestinal ischemia (30 minutes) followed by reperfusion (30 minutes). Using a factorial design, rats were randomized to receive local tissue perfusion with either normal saline or a 20% glycine solution during either the preischemia or the prereperfusion phase. Standardized segments of small intestine were removed at the end of the study period to determine the extent of ischemia-reperfusion injury. RESULTS: Perfusion with 20% glycine increased mucosal protein content (p < .05), increased mucosal DNA content (p < .05), reduced intestinal myeloperoxidase activity (p < .05), and maintained mucosal glutaminase activity. This was true regardless of whether glycine was administered during the preischemia phase or the prereperfusion phase. CONCLUSIONS: Local perfusion with 20% glycine can diminish warm ischemia-reperfusion injury to the rat small intestine in an in vivo model. The role of glycine supplementation should be evaluated in situations where hemodynamic instability may be responsible for breakdown in the gut barrier.

The management of patients with the short bowel syndrome.

The surgeon is invariably the primary specialist involved in managing patients with short bowel syndrome. Because of this they will play an important role in co-ordinating the management of these patients. The principal aims at the initial surgery are to preserve life, then to preserve gut length, and maintain its continuity. In the immediate postoperative period, there needs to be a balance between keeping the patient alive through the use of TPN and antisecretory agents and promoting gut adaptation with the use of oral nutrition. If the gut fails to adapt during this period, then the patient may require therapy with more specific agents to promote gut adaptation such as growth factors and glutamine. If following this, the patient still has a short gut syndrome, then the principal options remain either long term TPN, or intestinal transplantation which remains a difficult and challenging procedure with a high mortality and morbidity due to rejection.