The effect of vitamin E and selenium on doxorubicin (Adriamycin) induced delayed toxicity in mice.
The antagonistic action of repeated administration of vitamin E and selenium on the lethality caused by a single intraperitoneal injection of doxorubicin 15 to 20 mg/kg has been investigated in mice. Mice were treated with vitamin E, 20 to 4100 mg/kg intraperitoneally/intramuscularly daily or once a week and/or selenium 27 micrograms/kg orally daily for 6 to 7 weeks, i.e. one or two weeks before and five weeks after doxorubicin administration. 30 mg/kg of doxorubicin intraperitoneally caused 100% lethality within 4 days, whereas 15 mg/kg caused no deaths within a week, but resulted in a delayed toxicity with a cumulative lethality of 80% at the end of the observation period of 6 months. Vitamin E protected the mice from the lethal effect of doxorubicin, 15 mg/kg during the administration, but the mice began to die when the vitamin E administration was discontinued. Selenium only protected the mice for two weeks in spite of the continuous administration of selenium. The combined administration of vitamin E and selenium had no protective effect on the lethality caused by doxorubicin, 20 mg/kg. The pathogenesis of the delayed lethality of a single doxorubicin administration in mice is discussed. It is concluded that vitamin E and/or selenium have no significant protective action against doxorubicin induced delayed lethality in mice.
D000284:Administration, Oral; D000818:Animals; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D005609:Free Radicals; D006321:Heart / Q000187:drug effects; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
D005609:Free Radicals; D014810:Vitamin E; D004317:Doxorubicin; D012643:Selenium