Iron overload in the rat pancreas following portacaval shunting and dietary iron supplementation.
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.
Horne
W I
WI
Department of Medicine, Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio 44109, USA.
Tandler
B
B
Dubick
M A
MA
Niemelä
O
O
Brittenham
G M
GM
Tsukamoto
H
H
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
D000447:Aldehydes; D019266:Iron, Dietary; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal