Short-term malnutrition in neonatal rabbits: effect on function and synthesis of free radical metabolizing enzymes in the gastrointestinal tract.

Oxygen-derived free radicals are an important component of gastrointestinal injury in necrotizing enterocolitis (NEC). To assess the effect of a 72-h fast on the ability of neonatal small bowel to metabolize free radicals, the activity of superoxide dismutase (SOD), catalase, and the glutathione cycle were quantitated in mucosal scrapings from proximal and distal small bowel of fed and fasted neonatal rabbits. Hexose monophosphate shunt activity, quantitated in enterocytes from fed and fasted neonatal rabbits, was significantly less, p less than 0.01, in fasted animals. SOD activity was lower in distal small bowel from fasted animals than fed. The two mechanisms available to metabolize H2O2, catalase and the glutathione cycle, were significantly lower in both proximal and distal small bowel from fasted animals than in those from fed animals. To determine if fasting caused decreased enzyme activity at the level of gene expression, gastrointestinal tract DNA, RNA and protein, and specific mRNA levels for catalase, glutathione peroxidase (GPx), and SOD were quantitated. DNA, total RNA, and mRNA for SOD were lower in mucosal scrapings from fasted animals. However, mRNA for catalase, and GPx were not lower in fasted animals. Thus, a 72-h fast in neonatal rabbits causes a regional-specific decrease in SOD activity, which may be explained by decreased transcription. Changes in transcription do not completely account for regulation of catalase and glutathione cycle enzymes.