Effects of a water-soluble prodrug of vitamin E on doxorubicin-induced toxicity in mice.
Effects of the administration of a water-soluble prodrug of vitamin E on doxorubicine (DXR)-induced lethal and oxidative toxicity in mice were studied. The prodrug used was d-alpha-tocopheryl N,N-dimethylaminoacetate hydrochloride (TDMA). It was intravenously administered to animals 2 h prior to an intraperitoneal administration of DXR (15 mg/kg). The single preadministration of the prodrug (10-50 mg/kg equivalent for d-alpha-tocopherol) delayed the DXR-induced death and the ameliorative effect was TDMA-dose dependent. The extent of total lipid peroxidation of the heart and liver was assessed by 2-thiobarbituric acid reactant substance levels. DXR significantly accelerated lipid peroxidation in the liver but not in the heart. The elevation of liver lipid peroxide was significantly suppressed to a normal range by a single preadministration of TDMA (50 mg/kg equivalent for d-alpha-tocopherol). TDMA did not significantly affect the antitumor activity of DXR in mice inoculated with L1210 leukemia cells.
Nagata
Y
Y
Kyoritsu College of Pharmacy, Tokyo, Japan.
Takata
J
J
Karube
Y
Y
Matsushima
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D004317:Doxorubicin / Q000627:therapeutic use / Q000633:toxicity*; D004359:Drug Therapy, Combination; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007939:Leukemia L1210; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology; D012995:Solubility; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D014867:Water
D000970:Antineoplastic Agents; D011355:Prodrugs; D020011:Protective Agents; C121469:tocopheryl N,N-dimethylaminoacetate; D014867:Water; D014810:Vitamin E; D004317:Doxorubicin; D005998:Glycine