Metabolism of Superoxide Dismutase during the Adynamic Ileus of Endotoxemia

Endotoxemia is accompanied by gastrointestinal motor disturbances while administration of oxygen free radical scavengers following endotoxemia ameliorates these motor disturbances. We hypothesized that the motor disturbance produced by endotoxemia may be associated with a change in the activity or production of superoxide dismutase (SOD). Strain gauge transducers were placed on the stomach and small bowel of dogs to determine fasting gastrointestinal motility. Manganese and copper/zinc SOD enzyme activities in gut smooth muscle were measured and protein expression was analyzed by Western blotting. Following completion of the baseline studies, dogs were given a single dose of Escherichia coli lipopolysaccharide, 200 µg/kg i.v., and the studies repeated for the next 3 days. Following endotoxin bolus, the migrating motor complex (MMC) was delayed for 2 days while gastric and jejunal smooth muscle levels of Cu/Zn SOD activity were decreased for 1 day in the stomach and for 2 days in the jejunum. Western blotting indicated that endotoxin did not change the amount of SOD enzyme produced. We conclude that endotoxemia results in a temporary prolongation of the MMC and a decrease in Cu/Zn SOD activity. Expression of Cu/Zn SOD and Mn SOD does not seem suppressed by endotoxin as measured by Western blotting. However, the impairment of Cu/Zn SOD activity may contribute to ileus associated with sepsis by altering oxygen-free metabolism in both the stomach and jejunum.