title: Iron overload in the rat pancreas following portacaval shunting and dietary iron supplementation.
abstract: Reproduction of pancreatic iron overload in an animal model has been difficult to achieve primarily because of the first-pass extraction of iron by the liver. We hypothesized that portacaval shunting would avoid this hepatic phenomenon and increase pancreatic iron deposition. An end-to-side portacaval shunt was surgically created in male Sprague-Dawley rats, and they were subsequently fed a carbonyl iron-supplemented diet for 17 weeks. This resulted in marked iron accumulation in the pancreas (1621 +/- 188 micrograms/g) compared to minimal deposition in sham-operated rats fed the same diet (138 +/- 53 micrograms/g). Iron deposition in the acinar and centroacinar cells was confirmed histologically by Gomori staining, as well as by ultrastructural examination. Iron overloading was associated with enhanced oxidative stress evidenced by a twofold increase in the levels of glutathione disulfide and thiobarbituric acid-reactive substances. Also, adducts of proteins with malondialdehyde and 4-hydroxynonenal were demonstrated in acinar and ductal cells. Other apparent consequences of iron overload were a 50% reduction in pancreatic amylase content and a decrease in pancreatic protein concentration. These hypotrophic changes were associated with a reduced mass of zymogen granules in the acinar cells noted histologically. Our results show that a combination of portacaval shunting and carbonyl iron feeding achieve pancreatic iron overload and support the role of oxidative stress in the pathogenesis of iron-induced damage in the pancreas.
authors.affiliation: Department of Medicine, Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio 44109, USA.
authors.forename: W I
authors.initials: WI
authors.lastname: Horne
authors.forename: B
authors.initials: B
authors.lastname: Tandler
authors.forename: M A
authors.initials: MA
authors.lastname: Dubick
authors.forename: O
authors.initials: O
authors.lastname: Niemelä
authors.forename: G M
authors.initials: GM
authors.lastname: Brittenham
authors.forename: H
authors.initials: H
authors.lastname: Tsukamoto
mesh_terms: D000447:Aldehydes / Q000032:analysis; D000818:Animals; D019587:Dietary Supplements; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D019190:Iron Overload / Q000473:pathology / Q000503:physiopathology*; D019266:Iron, Dietary / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress; D010179:Pancreas / Q000473:pathology*; D010182:Pancreatic Diseases / Q000473:pathology / Q000503:physiopathology*; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000447:Aldehydes; D019266:Iron, Dietary; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal