A tungsten-supplemented diet delivered by transplacental and breast-feeding routes lowers intestinal xanthine oxidase activity and affords cytoprotection in ischemia-reperfusion injury to the small intestine

Abstract

Ischemia-reperfusion injury has been implicated as playing a major role in the development of necrotizing enterocolitis, a major cause of morbidity and mortality in the newborn. A tungsten-supplemented molybdenum-free diet can reduce xanthine oxidase (XO) enzyme activity in the intestine, which in turn reduces the generation of oxygen radicals after an ischemia-reperfusion insult. This study evaluated the ability of this diet to be effective by indirect means, ie, transplacental and breast-feeding routes. XO activity of the intestine was measured in three groups of CD-1 white rats: I, weanlings fed the tungsten diet or standard chow for 1 week; II, 1-day-old rat pups whose mothers were maintained on the tungsten or standard chow for 7 to 10 days prior to term; and III, rat pups at 1 and 3 weeks after birth whose lactating mothers were maintained on the tungsten or standard chow. Some animals from group III also underwent either a 30- or 60-minute episode of occlusion of the superior mesenteric artery (SMA) to evaluate the protective effects of the diet. XO activity was significantly reduced in all groups receiving the tungsten diet ( P < .0001). Blinded histopathologic studies of the entire small bowel showed significantly less villar necrosis ( P < .05) and fibrosis ( P < .0001) in the tungsten-treated group than in the controls. In the 60-minute occlusion study all tungsten-group animals survived, whereas 7 of 12 in the control group died of intestinal infarction within 24 hours ( P < .001). These results indicate that XO activity can be lowered by a tungsten-supplemented molybdenum-free diet delivered by indirect routes. The ability to transfer the effect of the diet via the transplacental and breast-feeding routes has not been previously reported. The protective effect of the diet via breast-feeding further supports the role of ischemia-reperfusion injury as a major contributing factor to the development of necrotizing enterocolitis and loss of mucosal barrier function, and suggests areas of future research for possible prophylactic treatment of ischemia-reperfusion intestinal injuries.