Early appearance of age-associated deterioration in mitochondrial function of diaphragm and heart in rats treated with doxorubicin.
Age-associated deterioration of mitochondrial energy transduction seems to be a major contributory factor to age-related decline in organ function. Free radicals are likely to be involved in the age-related decline in mitochondrial function. This study was designed to elucidate whether or not doxorubicin, a radical generating drug that was administered to 7-week-old rats, affects age-associated mitochondrial functional changes in diaphragm, heart, and liver. Mitochondria from each tissue were prepared from rats aged 7, 13, 20, 28, 35, and 55 weeks, and the activities of four complexes in the mitochondrial energy transduction system were measured enzymatically. In diaphragm mitochondria of the control group, the complex I activity in 28-week-old rats declined to 82% of the activity in rats aged 7 weeks, and the complex IV activity in 55-week-old rats declined to 70% of the activity in rats aged 7 weeks. On the contrary, a significant decrease in the activity of complex I in rats aged 20 weeks (84%) and that of complex IV in rats aged 35 weeks (86%) were observed in the doxorubicin-treated group. In heart mitochondria, age-related changes in activities of complexes I and IV did not appear in rats aged up to 55 weeks, whereas significant decreases in the activities of complexes I (78%) and IV (90%) were observed in rats aged 35 weeks in the doxorubicin group. Age-related changes in liver mitochondria were not found in rats aged up to 55 weeks, and no deleterious effects of doxorubicin were observed in liver mitochondrial function. From these results, the early appearance of aging effects on mitochondrial function was observed in rats treated with doxorubicin particularly in postmitotic cells.
Yamada
K
K
Department of Biomedical Chemistry, University of Nagoya, Japan.
Sugiyama
S
S
Kosaka
K
K
Hayakawa
M
M
Ozawa
T
T
D000375:Aging / Q000502:physiology*; D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism*; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D004317:Doxorubicin