Presence of iron catalytic for free radical reactions in patients undergoing chemotherapy: implications for therapeutic management.
We investigated the kinetics of generation of iron 'catalytic' for free radical reactions in children with diagnosed acute lymphoblastic leukaemia (ALL) who received high-dose methotrexate infusions. In 76% of the chemotherapy courses studied, 'catalytic' iron appeared in plasma in the concentration range from 0.1 to 3 mumol/l. Positive correlations between maximum levels of 'catalytic' iron and plasma hepatic enzymes could be established in the majority of cases and in one subset of patients (low and medium risk ALL) mean 'catalytic' iron levels correlated well to clinically observable toxicities. The damaging potential of 'catalytic' iron was also demonstrated experimentally: oxidative damage to proteins was significantly (P < 0.05) higher in plasma samples showing the presence of 'catalytic' iron and in addition a strong correlation (r = 0.95, P < 0.02) was seen between plasma concentration of 'catalytic' iron and the ability of the plasma to stimulate lipid peroxidation. Our data show that chemotherapy releases 'catalytic' iron which may relate to toxic side effects. Hence binding this 'catalytic' iron by judicious co-administration of iron chelating agents could be beneficial in minimizing the iatrogenic adverse effects of chemotherapy of acute leukaemia.
Carmine
T C
TC
Pharmacology Group, King's College, London, UK.
Evans
P
P
Bruchelt
G
G
Evans
R
R
Handgretinger
R
R
Niethammer
D
D
Halliwell
B
B
D000293:Adolescent; D001761:Bleomycin; D002051:Burkitt Lymphoma / Q000097:blood / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007501:Iron / Q000097:blood*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy; D012189:Retrospective Studies
D001761:Bleomycin; D007501:Iron; D008727:Methotrexate