In hepatic iron overload, iron-catalyzed lipid peroxidation has been implicated in the mechanisms of hepatocellular injury. Lipid peroxidation may produce reactive aldehydes such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which may form aldehyde-protein adducts. We investipted whether lipid peroxidation occurred in rats fed a diet contain-ing 3% carbonyl iron for 5-13 wk, and if this resulted in the formation of MDA-and 4-HNE-protein adducts. Chronic iron feeding resulted in hepatic iron overload (> 10-fold) and con-comitantly induced a 2-fold increase in hepatic lipid peroxida-tion. Using an antiserum specific for MDA-lysine protein ad-ducts, we demonstrated by immunohistochemistry the pres-ence of aldehyde-protein adducts in the cytosol of periportal hepatocytes, which co-localized with iron. In addition, MDA-and 4-HNE-lysine adducts were found in plasma proteins of animals with iron overload. Only MDA adducts were detected in albumin, while other plasma proteins including a 120-kD protein had both MDA and 4-HNE adducts. In this animal model of hepatic iron overload, injury occurs primarily in peri-portal hepatocytes, where MDA-lysine protein adducts and excess iron co-localized. (J.
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