Study on the involvement of Zinc in homeostasis under intestinal Inflammation
Authors: Otsuka Yuuki , Tsujii Taisei , Amagase Kikuko 
Published: May 2023

Background & Aim: Zinc is one of the essential trace elements, and adequate amounts of zinc are crucial for good health. It is thought that zinc is absorbed primarily in the small intestine and also plays an important role in maintaining intestinal homeostasis. Small intestine is a key organ involved in digestion/absorption and is also sensitive to intestinal bacteria and easily inflamed. Alkaline phosphatase (ALP), which has zinc as its active center, detoxifies lipopolysaccharide and is thought to be involved in the suppression of small intestinal inflammation. In this study, we investigated the role of zinc in small intestinal inflammation using a mouse model, as well as the transporters ZIP4 and ZIP14, which are involved in ALP and zinc absorption. Materials & Methods: Male ICR mice were used. Indomethacin (IM, 12 mg/kg s.c.) was administered to mice to induce small intestinal inflammation. Four days prior to IM administration, zinc sulfate heptahydrate (Zn) was administered twice daily for 6 days. Forty-eight hours after IM administration, the animals were sacrificed and the lesion area was measured. Hematoxylin and eosin staining was performed. Myeloperoxidase (MPO) activity in the ileum was measured as an indicator of the degree of inflammation. ZIP4 and ZIP14 mRNA expression levels were examined by RT-PCR. ALP activity of the ileal was examined. IEC-6 cells, a rat small intestinal epithelial cell line, were seeded in 96-well plates, and Zn was applied 24 hours after seeding, and IM was added 24 hours after seeding. Cell viability was measured 24 hours after the addition of IM. Results: After administration of IM, bloody stools were observed from 24 hours after administration. At 48 hours after IM administration, disruption of villi structure and shortening of small intestine length were observed in the jejunum and ileum, and MPO activity was significantly increased. ZIP4 and ZIP14 mRNA expression levels were decreased in the small intestine 48 hours after IM treatment, and ALP activity was increased compared to the Vehicle group. On the other hand, pretreatment with Zn suppressed the occurrence of small intestinal inflammation, and the disruption of small intestinal villi structure was weak. The increase in MPO activity induced by IM tended to be suppressed by Zn pre-administration. ZIP4 and ZIP14 mRNA expression in Zn pre-administration group was same as in the IM alone group, and ALP activity was higher than in the IM alone group. IM treatment of IEC-6 also decreased cell viability in a concentration-dependent manner, which was inhibited by pretreatment with Zn in a concentration-dependent manner. Conclusion: These results suggest that zinc is effective in preventing the occurrence of NSAID-induced small intestinal inflammation. ZIP4 and ZIP14 are normally highly expressed in the intestinal epithelium and contribute greatly to zinc absorption, but the amount of zinc absorption may be decreased during inflammation induc University This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.