Oxygen Free Radical-Induced Histamine Release during Intestinal Ischemia and Reperfusion

Abstract

Acute mesenteric ischemia is highly lethal and therefore a serious problem for surgery and intensive care medicine; accordingly its pathophysiology warrants further study. Oxygen free radicals (OFR) play a role in the intestinal mucosal damage that develops during reperfusion after ischemia. Histamine (H) is generally released in various types of tissue ischemia. The link between H release and OFR has only been studied in in vitro systems. We tested the hypothesis that OFR may be involved in H release following reperfusion of the ischemic gut. The artery supplying a segment of the ileum was occluded for 1 or 2 h in anesthetized dogs. On reperfusion, a release of H into the venous effluent of the segment was demonstrated. Pretreatment of the animals with allopurinol (an inhibitor of xanthine oxidase), or with MTDQ-DA [6,6’-methylenebis(2,2-dimethyl-4-methanesulfonic acid sodium-1,2-dihydroquinoline)], a superoxide anion scavenger, or with a combination of allopurinol and MTDQ-DA resulted in an inhibition of H release. We conclude that OFR may play a role in the local H release following intestinal ischemia.

Role of Complement Activation and Mast Cell Degranulation in the Pathogenesis of Rapid Intestinal Ischemia/Reperfusion Injury in Rats

“…It is well recognized that disruption of the mucosal barrier causes sepsis, leading to multiple organ failure [1, 2, 3]. The prevention of intestinal I/R-induced mucosal injury would be a great advance in the prognosis of small bowel transplantation in the future.…”

“…Interestingly, the treatment with K-76COONa significantly blocked the MMC degranulation induced by rapid I/R-treatment. Since activated MMCs release preformed chemical mediators, including histamine [1, 2], leukotrienes [13], and platelet-activating factor [3]within 15 s after stimulation, it is possible that part of the tissue injury observed in this model may be mediated by release of these factors. Since complement-derived anaphylatoxins such as C5a are potent activators of mast cells [14, 15, 16], it should be noted that MMC activation is closely associated with the rapid generation of complement-derived anaphylatoxins.…”

“…The intestinal mucosa is constantly exposed to microcirculatory hypoxia and reoxygenation due to various stresses, and active oxygen and free radicals generated through these processes cause tissue damages in the intestine [1]. Ischemia-reperfusion (I/R) of the small bowel is associated with both increased microvascular permeability and mucosal barrier dysfunction, resulting in systemic shock under clinical and experimental conditions [1, 2, 3]. However, the precise mechanisms mediating I/R-induced mucosal barrier dysfunction have not fully been understood.…”

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

“…Most of the early studies are reviewed in Schoenberg and Beger (1993). XO-derived superoxide may trigger histamine release in the reperfused gut (Boros et al, 1989). Protection against gut reperfusion injury can also be achieved by inhibition of XO by tungsten (Pitt et al, 1991).…”

Pathogenic Importance of Cysteinyl Leukotrienes in Development of Gastric Lesions Induced by Ischemia/Reperfusion in Mice

“…The phenomenon of I/R injury is a major clinical problem after stroke, infarction, shock, and organ transplantation (Boros et al, 1989;Stein et al, 1990). The depletion of ATP and disturbance of intracellular Ca 2ϩ homeostasis have been suggested as the major pathophysiological mechanism during ischemia, leading to loss of cell viability (Farber et al, 1981;Cheung et al, 1986).…”