Decreased zinc absorption in guinea pig models of acute and chronic ileitis

Abstract

The biochemical defects underlying decreased Zn absorption in inflammatory bowel disease have not been identified. In vitro studies have suggested that reactive oxygen species (e.g., hypochlorous acid and superoxide), produced by phagocytic cells during the inflammatory response, mobilize Zn from metallothionein (MT) and other proteins that bind Zn via sulfhydryl groups. We avaluated the in vivo effects of intestinal inflammation on Zn absorption and Zn binding to intestinal MT and cysteine-rich intestinal protein (CRIP), possible components of a carrier-mediated intestinal Zn transport system. Guinea pig models of acute (NaOCl luminal perfusion) and chronic (2,4,6-trinitrobenzene sulfonic acid [TNBS] injection) ileitis were used. The rate of 65Zn absorption from the isolated ileum and the molecular distribution of 65Zn in mucosal cytosol determined by size-exclusion HPLC were measured after 1 hr of perfusion in the acute model and after 7 days in the chronic model. Zinc absorption was significantly lower in guinea pigs with either chronic or acute inflammation. In both models, decreased binding of 65Zn to MT and CRIP was also observed. The results indicate that decreased Zn absorption during intestinal inflammation may be mediated by the effects of oxidants on the transport activity of intestinal proteins that bind Zn via sulfhydryl groups.