Effect of doxorubicin on lipid peroxide levels in tissues of mice.
The tissue concentrations of doxorubicin (DOX, 15 mg/kg, ip) and daunorubicin (DAU, 15 mg/kg, ip) in mice were investigated to clarify their relationship to the cardiotoxicity, which is considered to be closely related to the lipid peroxide level in the heart. The largest Cmax of DOX after intraperitoneal injection was obtained in the liver and was equivalent to 1.8 times that in the heart. Elimination of DOX from the heart was not delayed. Nevertheless, the increases of lipid peroxide in the heart found in in vivo and in vitro experiments were considerably higher than those in the liver. Therefore, the cardiotoxicity of DOX can not be explained simply in terms of the relative concentrations of DOX in various tissues. On the other hand, experiments on the tissue concentration of DAU, which shows weaker cardiotoxicity than DOX, and on lipid peroxidation in vitro, suggested that the relative cardiotoxicities of DOX and DAU are directly related to their relative concentrations in the mouse heart. We observed a metabolite of DOX, doxorubicinone, and an unknown metabolite of DAU in various tissues of mouse after drug injection, but these metabolites did not seem to be involved in the cardiotoxicities of DOX and DAU.
D000818:Animals; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D006321:Heart / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D014018:Tissue Distribution
D008054:Lipid Peroxides; D004317:Doxorubicin; D003630:Daunorubicin