Oxidative stress in mouse heart by antitumoral drugs: a comparative study of doxorubicin and mitoxantrone.
Doxorubicin and mitoxantrone were given to mice in a single dose of 15 mg/kg body wt (i.p.). 'In situ' heart spontaneous chemiluminescence, hydroperoxide-initiated chemiluminescence and TBARS were measured in heart homogenates of treated and control animals at 2-5 days after injection. Heart spontaneous emission (control value: 45 +/- 5 cps/cm2) was increased by 10-fold in doxorubicin-treated mice 4 days after administration, whereas mitoxantrone did not produce any significant change. Administration of doxorubicin produced increases of 50% in hydroperoxide-initiated chemiluminescence and of 80% in TBARS levels 4 days after injection. Mitoxantrone did not induce significant changes in these parameters as compared with the controls. Cardiac reduced glutathione levels were not affected by mitoxantrone but were decreased (about 30%) by doxorubicin (control value: 0.98 +/- 0.08 mumol/g organ). Our data indicate that mitoxantrone does not induce an increase in the endogenous lipoperoxidation rate in heart tissue as doxorubicin does; this could contribute to the lower cardiotoxicity of mitoxantrone as compared with doxorubicin.
Lores Arnaiz
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Institute of Biochemistry and Biophysics, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Llesuy
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D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000032:analysis; D006321:Heart / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D051379:Mice; D008942:Mitoxantrone / Q000008:administration & dosage / Q000633:toxicity*; D009206:Myocardium / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D017392:Thiobarbituric Acid Reactive Substances; D004317:Doxorubicin; D008942:Mitoxantrone; D005978:Glutathione