Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload.
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 investigated whether lipid peroxidation occurred in rats fed a diet containing 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 (greater than 10-fold) and concomitantly induced a 2-fold increase in hepatic lipid peroxidation. Using an antiserum specific for MDA-lysine protein adducts, we demonstrated by immunohistochemistry the presence 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 approximately 120-kD protein had both MDA and 4-HNE adducts. In this animal model of hepatic iron overload, injury occurs primarily in periportal hepatocytes, where MDA-lysine protein adducts and excess iron co-localized.
Houglum
K
K
Department of Medicine, Veterans Administration Medical Center, San Diego, California.
Filip
M
M
Witztum
J L
JL
Chojkier
M
M
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D015180:Electrophoresis, Gel, Two-Dimensional; D005453:Fluorescence; D007501:Iron / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D008970:Molecular Weight; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013858:Thiobarbiturates / Q000378:metabolism
D000447:Aldehydes; D008054:Lipid Peroxides; D011506:Proteins; D013858:Thiobarbiturates; D008315:Malondialdehyde; D007501:Iron; C027576:4-hydroxy-2-nonenal; D008239:Lysine; C029684:thiobarbituric acid