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 do xorubicine (DXR)-induced lethal and oxidative toxicity in mice were studied . The prodrug used was d-alpha-tocopheryl N,N-dimethylaminoacetate hydrochl oride (TDMA), It was intravenously administered to animals 2 h prior to an intraperitoneal administration of DXR (15 mg/kg), The single preadministrat ion 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 a-thiobarbituric acid reactant substance levels, DXR significantly accel erated 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-tocopher ol). TDMA did not significantly affect the antitumor activity of DXR in mic e inoculated with L1210 leukemia cells.