Role of oxygen radicals in ischemic bowel disorders

Abstract

Major consequences of ischemic bowel disorders are: enhanced transcapillary filtration, interstitial edema, and sequestration of fluid in the lumen of the bowel. Although several endogenous substances (histamine, prostaglandine, etc.) are released from the small bowel, specific inhibitors do not prevent increased intestinal vascular premeability produced by ischemia reperfusion. Cytotoxic oxygen metabolites — so-called oxygen free radicals — are generated in excess after ischemia during the early reperfusion period and endogenous defense mechanisms are overwhelmed. The highly reactive oxygen radicals damage proteins, lipids, carbohydrates, and nucleotides. Experimental studies showed that pretreatment with oxygen free radical scavengers (super-oxide dismutase, catalase, dimethylsulfoxide) provided significant protection againts ischemic injuries to the small bowel. Further studies gave evidence that the enzyme xanthine oxidase, which reacts with hypoxanthine, constitutes the primary source of oxygen radical production after intestinal ischemia. Xanthine oxidase inhibitors (allopurinol, pterin aldehyde) are powerful substances attenuating the ischemia-induced increase in intestinal vascular permeability. Morphometric studies on biopsies obtained after reperfusion of the intestine indicated likewise that pretreatment with superoxide dismutase, allopurinol, etc. largely prevented the typical intestinal epithelial necrosis induced by ischemia reperfusion. The experimental results are promising for further clinical research. It is conceivable that drugs such as allopurinol or superoxide dismutase may become useful as a treatment of ischemic gastrointestinal diseases, such as necrotizing enterocolitis, volvulus, and others.