Sadzuka Y, Takino Y
School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Chem Pharm Bull (Tokyo). 1992 May;40(5):1329-31. doi: 10.1248/cpb.40.1329.
Lipid peroxide levels were measured in mouse tissues to study their relation to the cardiotoxicity of anthracyclines. The effects of tetrahydropyranyladriamycin (THP-ADR) and 4'-epiadriamycin (4'-epi-ADR), which are less cardiotoxic than adriamycin (ADR), were examined. Neither THP-ADR nor 4'-epi-ADR increased the lipid peroxide levels in the heart, however, both increased reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent lipid peroxidation in mouse liver and lung microsomes, to the same degree as ADR. Therefore, the results obtained in vitro were not the same as those obtained in vivo. Of all of the anthracyclines tested, only THP-ADR increased the lipid peroxide levels in the lung. Thus, THP-ADR may be pulmotoxic. Differences in the activities of glutathione peroxidase and glutathione S-transferase reflected the differences in lipid peroxide levels.
通过测量小鼠组织中的脂质过氧化物水平来研究它们与蒽环类药物心脏毒性的关系。研究了四氢吡喃阿霉素（THP-ADR）和4'-表阿霉素（4'-epi-ADR）的作用，它们的心脏毒性比阿霉素（ADR）小。然而，THP-ADR和4'-epi-ADR均未增加心脏中的脂质过氧化物水平，但二者均增加了小鼠肝脏和肺微粒体中依赖于还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的脂质过氧化作用，且程度与ADR相同。因此，体外获得的结果与体内获得的结果不同。在所有测试的蒽环类药物中，只有THP-ADR增加了肺中的脂质过氧化物水平。因此，THP-ADR可能具有肺毒性。谷胱甘肽过氧化物酶和谷胱甘肽S-转移酶活性的差异反映了脂质过氧化物水平的差异。
