Effect of high dose alpha-tocopherol and alpha-tocopherol acetate pretreatment on adriamycin (doxorubicin) induced toxicity and tissue distribution.
When two doses (15 mg/kg) of adriamycin (ADM) were administered to ICR mice pretreated with 500 mg/kg/day of alpha-tocopherol (VE) and alpha-tocopherol acetate (VE-AC) respectively, both the VE and the VE-AC pretreatment groups showed a significant shortening of survival time compared to control group. The concentration of ADM and of total aglycone (AD-NE) was determined in the tissue of mice given a single dose of 15 mg/kg of ADM after pretreatment with 500 mg/kg of VE and VE-AC, respectively, high values were found in liver, kidney and heart tissue compared to the control group. And, particularly the heart tissue of the group pretreated with VE showed significantly higher values of ADM and AD-NE. High AD-NE levels were noted in mouse liver mitochondria (Mt), after pretreatment with both VE and VE-AC, with a significantly higher concentration in the VE-pretreated group. A comparison of the uptake of ADM and AD-NE into mouse Mt pretreated with VE or VE-AC in vitro, showed no difference in the ADM value from that of the control group, but both the VE- and the VE-AC-pretreated groups had significantly higher in AD-NE concentrations compared to the control group.
Shinozawa
S
S
Department of Hospital Pharmacy, Okayama University Medical School, Japan.
Gomita
Y
Y
Araki
Y
Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000633:toxicity*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism; D014018:Tissue Distribution; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
D014810:Vitamin E; D004317:Doxorubicin; D024502:alpha-Tocopherol; D024505:Tocopherols