Iron-induced oxidant stress leads to irreversible mitochondrial dysfunctions and fibrosis in the liver of chronic iron-dosed gerbils. The effect of silybin.
Hepatic iron toxicity because of iron overload seems to be mediated by lipid peroxidation of biological membranes and the associated organelle dysfunctions. However, the basic mechanisms underlying this process in vivo are still little understood. Gerbils were dosed with weekly injections of iron-dextran alone or in combination with sylibin, a well-known antioxidant, by gavage for 8 weeks. A strict correlation was found between lipid peroxidation and the level of desferrioxamine chelatable iron pool. A consequent derangement in the mitochondrial energy-transducing capability, resulting from a reduction in the respiratory chain enzyme activities, occurred. These irreversible oxidative anomalies brought about a dramatic drop in tissue ATP level. The mitochondrial oxidative derangement was associated with the development of fibrosis in the hepatic tissue. Silybin administration significantly reduced both functional anomalies and the fibrotic process by chelating desferrioxamine chelatable iron.
Masini
A
A
Sezione di Patologia Generale, Dipartimento di Scienze Biomediche Universita di Modena, Italy. masini@unimo.it
Ceccarelli
D
D
Giovannini
F
F
Montosi
G
G
Garuti
C
C
Pietrangelo
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D005849:Gerbillinae; D007501:Iron / Q000009:adverse effects* / Q000378:metabolism; D019190:Iron Overload / Q000378:metabolism / Q000517:prevention & control*; D007505:Iron-Dextran Complex / Q000008:administration & dosage / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016877:Oxidants / Q000009:adverse effects* / Q000378:metabolism; D018384:Oxidative Stress; D012838:Silymarin / Q000494:pharmacology*
D000975:Antioxidants; D016877:Oxidants; D012838:Silymarin; D000255:Adenosine Triphosphate; D007505:Iron-Dextran Complex; D007501:Iron