Sazuka Y, Yoshikawa K, Tanizawa H, Takino Y
Chem Pharm Bull (Tokyo). 1989 Dec;37(12):3412-5. doi: 10.1248/cpb.37.3412.
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.
我们以阿霉素（ADR）作为对照药物，检测了阿克拉霉素（ACM）处理的小鼠体内的脂质过氧化物水平。给予ACM（15mg/kg，腹腔注射）后3小时或4天时，心脏中的脂质过氧化物水平并未升高，而ADR处理的小鼠心脏中的脂质过氧化物水平升高至正常小鼠的257%。ACM及其糖苷型代谢产物对还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）依赖性微粒体脂质过氧化（体外）增加的作用比ADR弱。然后，我们检测了ACM在组织中的浓度。在所检测的组织中，ACM的AUC0-24h在心脏中最低，仅为ADR的29.3%。然而，所测定的ACM糖苷型代谢产物在所有组织中的浓度均高于ACM的浓度。在心脏中，ACM糖苷的T1/2和AUC0-24h略高于ADR。总之，ACM及其代谢产物不会导致小鼠心脏中脂质过氧化物水平升高，ADR和ACM诱导的小鼠心脏脂质过氧化物增加的差异与药物的组织浓度无关。
