[Effect of biological membrane stabilizing drugs (coenzyme Q10, dextran sulfate and reduced glutathione) on adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice].
The protective effects of the biological membrane stabilizing drugs, coenzyme Q10 (CoQ), dextran sulfate (DS) and reduced glutathione (GSH), on doxorubicin (adriamycin, ADM)-induced toxicity and microsomal lipid peroxidation were studied in mice. The mice administered ADM with combined treatment of CoQ, DS or GSH showed a significantly longer survival time than the ADM control group (which were injected with 15 mg/kg of ADM twice). The optimum protective doses of these drugs against ADM-induced toxicity were 10 mg/kg/day (p.o.) for CoQ, 100 mg/kg/day (s.c.) for DS and 100 mg/kg/day (i.p.) for GSH. The survival times of the mice (expressed as a percent of the treated group per control group) were 224.1% for CoQ, 220.7% for DS and 213.7% for GSH. The groups treated with these drugs showed a significant decrease in mouse liver and heart microsomal lipid peroxidation in comparison to that of the ADM control group. These results suggest that the heart microsomal lipid peroxidation levels may be one of the indications of ADM-induced cardiac toxicity. These drugs tested in the present study may stabilize the heart microsomal membrane lipid or may improve the myocardiac mitochondrial functions over those in ADM-treated mouse.
Dept. of Hospital Pharmacy, Okayama University Medical School.
S
S
Shinozawa
H
H
Kawasaki
Y
Y
Gomita
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D003067:Coenzymes; D016264:Dextran Sulfate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008861:Microsomes / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000931:Antidotes; D003067:Coenzymes; D014451:Ubiquinone; D004317:Doxorubicin; D016264:Dextran Sulfate; C024989:coenzyme Q10; D005978:Glutathione