Approaches that mitigate doxorubicin-induced delayed adverse effects on mitochondrial function in rat hearts; liposome-encapsulated doxorubicin or combination therapy with antioxidant.
This experiment was designed to evaluate whether or not liposomal encapsulated-doxorubicin and combination therapy of free doxorubicin with coenzyme Q10, an antioxidant, mitigate the delayed adverse effects on cardiac muscle mitochondria. Rats aged 7 weeks were divided into the following four groups; rats were injected with doxorubicin or liposomal encapsulated-doxorubicin, total dose 15 mg/kg. The doxorubicin group consisted of two subgroups depending on diet, i.e., standard diet or 0.2% coenzyme Q10 diet. Mitochondria from cardiac muscles were prepared from rats aged 13 and 35 weeks. No significant decrease in the activity of complex I of the mitochondrial electron transport chain was observed in rats aged 13 weeks among the groups, however, significant decreases in the activity in rats aged 35 weeks were observed in the doxorubicin and liposomal doxorubicin groups compared with the corresponding control rats. In contrast, no significant change in complex I activity was observed in rats fed with coenzyme Q10 diet irrespective of doxorubicin treatment. From these results, not liposomal encapsulation of doxorubicin but combination therapy with antioxidant might be expected to reduce the delayed adverse effects of doxorubicin on heart mitochondria.
Sugiyama
S
S
Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
Yamada
K
K
Hayakawa
M
M
Ozawa
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003067:Coenzymes; D004317:Doxorubicin / Q000633:toxicity*; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D004579:Electron Transport / Q000187:drug effects; D008081:Liposomes; D008929:Mitochondria, Heart / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D003067:Coenzymes; D004337:Drug Carriers; D008081:Liposomes; D014451:Ubiquinone; D004317:Doxorubicin; D010088:Oxidoreductases; D016660:NAD(P)H Dehydrogenase (Quinone); C024989:coenzyme Q10