[Effects of anthracycline drugs (aclarubicin, daunorubicin, doxorubicin, epirubicin, pirarubicin) on mouse acute toxicity and rat liver microsomal lipid peroxidation].
Effects of anthracycline type antitumor agents (aclarubicin, ACL; daunorubicin, DAU; doxorubicin, DOX; epirubicin, EPI; pirarubicin, PIR) on the acute toxicity to mouse, rat liver microsomal lipid peroxidation and mitochondrial functions in vitro were studied. ACL showed the least production of liver microsomal lipid peroxidation in all tested anthracyclines in the increasing order of PIR, DOX, DAU and EPI. The increase of production of lipid peroxidation induced by these drugs correlated well with the decrease in body weight of mice administered i.p. at 20 mg/kg and 50% lethal dose of these drugs. On the effect of mitochondrial function, all drugs tested decreased the oxygen uptake of state 3 and the level of respiratory control index. ACL showed the most severe inhibition of these functions in all drugs. These observations suggest that the degree of microsomal lipid peroxidation induced with the anthracycline drugs was related to the development of the drug acute toxicity.
Shinozawa
S
S
Dept. of Hospital Pharmacy, Okayama University Medical School, Japan.
Gomita
Y
Y
Araki
Y
Y
D015250:Aclarubicin / Q000633:toxicity; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003630:Daunorubicin / Q000633:toxicity; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000633:toxicity; D015251:Epirubicin / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D015250:Aclarubicin; D004317:Doxorubicin; C027260:pirarubicin; D003630:Daunorubicin