Effect of aclacinomycin on lipid peroxide levels in tissues of mice.
We have examined the lipid peroxide levels in aclacinomycin (ACM)-treated mice by using adriamycin (ADR) as a comparative drug. There was no increase in the lipid peroxide level of the heart at either 3h or 4d after ACM administration (15 mg/kg, i.p.), although the level in the heart of ADR-treated mice was elevated to 257% of that in normal mice. The effect of ACM and its glycoside-type metabolites on the increase of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent microsomal lipid peroxidation (in vitro) was weaker than that of ADR. Then, we examined the tissue concentrations of ACM. The AUC0-24h of ACM was the lowest in the heart among the tissues examined, being only 29.3% of that obtained with ADR. However, the concentrations of the glycoside-type metabolites of ACM in all tissues determined were higher than the concentration of ACM. In the heart, the T1/2 and AUC0-24h of ACM glycosides were somewhat higher than those of ADR. In conclusion, ACM and its metabolites do not lead to an increase in lipid peroxide level in the heart of mouse, and the difference in lipid peroxide increment in the mouse heart induced by ADR and ACM is independent of the tissue concentration of the drugs.
Sazuka
Y
Y
Yoshikawa
K
K
Tanizawa
H
H
Takino
Y
Y
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D008054:Lipid Peroxides / Q000378:metabolism*; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism
D008054:Lipid Peroxides; C011157:aclacinomycins; D015250:Aclarubicin