title: Systemic iron supplementation replenishes iron stores without enhancing colon carcinogenesis in murine models of ulcerative colitis: comparison with iron-enriched diet.
abstract: Ulcerative colitis (UC) patients frequently require iron supplementation to remedy anemia. The impact of systemic iron supplementation (intraperitoneal injection) on UC-associated carcinogenesis was assessed in mice subjected to cyclic dextran sulfate sodium (DSS) treatment and compared with dietary iron enrichment. Systemic iron supplementation, but not a twofold iron diet, remedied iron deficiency as indicated by the histochemical detection of splenic iron stores. A twofold iron diet, but not systemic iron, increased iron accumulation in colonic luminal contents, at the colonic mucosal surface, and in superficial epithelial cells. Colitis-associated colorectal tumor incidence after 15 DSS cycles was not affected by systemic iron (2/28; 7.1%) compared to nonsupplemented controls (4/28; 14.1%) but was significantly increased by the twofold iron diet (24/33; 72.7%) (P < 0.001). Mechanistic study revealed that systemic iron had no effect on DSS-induced inflammation, or colonic iNOS and COX-2 protein levels, compared to controls. Systemic iron supplementation for 16 weeks replenished splenic iron in a spontaneous colitis model (interleukin-2-deficient mice) and significantly reduced colonic inflammation compared to interleukin-2 (-/-) controls without increasing hyperplastic lesions. These results suggest that iron supplemented systemically could be used to remedy anemia in UC patients without exacerbating inflammation or enhancing colon cancer risk. These findings need to be verified in clinical studies.
authors.affiliation: Susan L Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854-8020, USA.
authors.forename: Darren N
authors.initials: DN
authors.lastname: Seril
authors.forename: Jie
authors.initials: J
authors.lastname: Liao
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology; D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology / Q000473:pathology; D051546:Cyclooxygenase 2; D016264:Dextran Sulfate; D019587:Dietary Supplements; D005260:Female; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000235:genetics; D007501:Iron / Q000008:administration & dosage* / Q000378:metabolism* / Q000494:pharmacology; D019266:Iron, Dietary / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D019266:Iron, Dietary; D016264:Dextran Sulfate; D007501:Iron; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases