Effect of exogenous heme on hepatic iron-load and changes induced in hepatic heme metabolism by chronic iron-load.
It has recently been shown that heme arginate treatment can markedly improve blood cell counts in some severely cytopenic patients with a myelodysplastic syndrome (MDS). As MDS is often associated with iron overload, we have now studied in iron-loaded rats the hepatic effects of heme arginate given in a dose of 1.2 mg/100 g intraperitoneally twice a week for a period of 4.5 weeks. The heme injections caused a very marked increase in the mean hepatic iron content of the iron-loaded rats, which was more than twice the total amount of the heme-iron injected per rat. The heme treatment did not significantly affect the activities of the enzymes involved in the heme metabolism. Although no clinical side effects have been found in the MDS patients treated with heme arginate so far, the present study suggests that in iron-load the possible adverse hepatic effects should be taken into account and a minimum therapeutic dose of heme arginate should be used.
Volin
L
L
Third Department of Medicine, University of Helsinki, Finland.
Vuori
E
E
Tenhunen
R
R
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006418:Heme / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D011506:Proteins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D007501:Iron