TABLE 1

Effect of metal chelators, radical scavengers, antioxidants, β-blockers, nitrone spin traps, and lipid-lowering drugs on the formation of anthracycline secondary alcohol metabolites by human heart cytosolic fractions

Experiments were performed by incubating cytosolic fractions (1 mg protein/ml) in standard buffer at 37°C with or without (vehicle) 100 μM of each compound added 5 minutes before DOX or DNR addition (50 μM, final concentration). Reactions were started by adding NADPH (250 μM, final concentration). Alcohol metabolites were assayed after 240 minutes at 37°C as described in Materials and Methods. Xenobiotic stock solutions were prepared just before use as follows: melatonin, all-trans-retinal, and α-tocopherol (5 mM) and carvedilol, lovastatin, and mevastatin (10 mM) in absolute ethanol; trolox, adenosine, and amifostine (5 mM) and dexrazoxane (12.5 mM) in standard buffer; and POBN and PBN (100 mM) in dimethyl sulfoxide. Values are the mean ± S.E. of at least three separate experiments performed in triplicate.

CompoundPercentage of Inhibition
DOXol FormationDNRol Formation
Dexrazoxane4 ± 55 ± 5
Melatonin3 ± 48 ± 5
α-tocopherol5 ± 26 ± 3
Trolox4 ± 28 ± 4
Amifostine4 ± 27 ± 4
Carvedilol8 ± 46 ± 4
Adenosine3 ± 25 ± 3
PBN3 ± 27 ± 4
POBN4 ± 35 ± 3
Lovastatin7 ± 45 ± 4
Mevastatin2 ± 23 ± 2
All-trans-retinal2 ± 429 ± 4
  • PBN, N-tert-butyl-α-phenylnitrone; POBN, α-(4-pyridyl, 1-oxide)-N-tert-butylnitrone.