title: An iron-deficient diet stimulates the onset of the hepatitis due to hepatic copper deposition in the Long-Evans Cinnamon (LEC) rat.
abstract: To study effects of dietary Cu and Fe levels on the onset of hepatitis in Long-Evans Cinnamon (LEC) rats, female rats (40 days old) were fed a semipurified diet containing 0.1 or 10 mg Cu/kg and 1.5 or 150 mg Fe/kg in a 2 x 2 factorial arrangement for 35 days. At 75 days after birth, LEC rats (+Cu-Fe) fed a Cu-sufficient but Fe-deficient diet (Cu, 10 mg/kg; Fe, 1.5 mg/kg) showed jaundice, with lethargy, anorexia, and malaise. The biochemical variables relating to liver function were significantly increased compared to three other groups, a Cu- and Fe-deficient (-Cu-Fe) group, a Cu-deficient but Fe-sufficient (-Cu+Fe) group, and a Cu and Fe sufficient (+Cu+Fe) group. Furthermore, the +Cu-Fe rat liver showed massive necrosis with huge nuclei. The other three groups presented no biochemical and histological findings of hepatitis. Hepatic Cu and metallothionein concentrations were 289 +/- 87 (mean +/- SD) microg/g liver and 8.7 +/- 1.8 mg/g liver, respectively, in the +Cu-Fe rats. However, in the +Cu+Fe group the values were 196 +/- 28 microg Cu/g liver and 10.8 +/- 1.0 mg/g liver. Hepatic Fe deposition was not influenced significantly by the dietary Cu level. The +Cu-Fe group with jaundice showed the highest free Cu concentration in the liver among the four groups, but the hepatic free Fe concentration was similar to those in the -Cu+Fe and +Cu+Fe groups. Our results indicate that an Fe-deficient diet enhances the deposition of hepatic Cu due to increased absorption of Cu from the gastrointestinal tract. This deposition stimulated the onset of hepatitis.
authors.affiliation: Department of Public Health, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Japan. sugawara@sapmed.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Sugawara
authors.forename: C
authors.initials: C
authors.lastname: Sugawara
mesh_terms: D000818:Animals; D001835:Body Weight; D003300:Copper / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D005293:Ferritins / Q000378:metabolism; D006520:Hepatitis, Animal / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006527:Hepatolenticular Degeneration / Q000378:metabolism; D007408:Intestinal Absorption; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000008:administration & dosage; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008668:Metallothionein / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013047:Specific Pathogen-Free Organisms
chemical_list: D019266:Iron, Dietary; D003300:Copper; D005293:Ferritins; D008668:Metallothionein; D007501:Iron