Attenuation of acute and chronic liver injury in rats by iron-deficient diet.
Oxidative stress due to iron deposition in hepatocytes or Kupffer cells contributes to the initiation and perpetuation of liver injury. The aim of this study was to clarify the association between dietary iron and liver injuries in rats. Liver injury was initiated by the administration of thioacetamide or ligation of the common bile duct in rats fed a control diet (CD) or iron-deficient diet (ID). In the acute liver injury model induced by thioacetamide, serum levels of aspartate aminotransferase and alanine aminotransferase, as well as hepatic levels of lipid peroxide and 4-hydroxynonenal, were significantly decreased in the ID group. The expression of 8-hydroxydeoxyguanosine and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling positivity showed a similar tendency. The expression of interleukin-1beta and monocyte chemotactic protein-1 mRNA was suppressed in the ID group. In liver fibrosis induced by an 8-wk thioacetamide administration, ID suppressed collagen deposition and smooth muscle alpha-actin expression. The expressions of collagen 1A2, transforming growth factor beta, and platelet-derived growth factor receptor beta mRNA were all significantly decreased in the ID group. Liver fibrosis was additionally suppressed in the bile-duct ligation model by ID. In culture experiments, deferoxamine attenuated the activation process of rat hepatic stellate cells, a dominant producer of collagen in the liver. In conclusion, reduced dietary iron is considered to be beneficial in improving acute and chronic liver injuries by reducing oxidative stress. The results obtained in this study support the clinical usefulness of an iron-reduced diet for the improvement of liver disorders induced by chronic hepatitis C and alcoholic/nonalcoholic steatohepatitis.
Otogawa
Kohji
K
Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno, Osaka, Japan.
Ogawa
Tomohiro
T
Shiga
Ryoko
R
Nakatani
Kazuki
K
Ikeda
Kazuo
K
Nakajima
Yuji
Y
Kawada
Norifumi
N
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018932:Chemokine CCL2 / Q000235:genetics; D002908:Chronic Disease; D003676:Deferoxamine / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000178:diet therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics; D017262:Siderophores / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D019266:Iron, Dietary; D012333:RNA, Messenger; D017262:Siderophores; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D020797:Receptor, Platelet-Derived Growth Factor beta; D020778:Matrix Metalloproteinase 2; D003676:Deferoxamine