Effects of a Water-Soluble Prodrug of Vitamin E on Doxorubicin-Induced Toxicity in Mice

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Effects of the administration of a water-soluble prodrung of vitamin E on doxorubicine (DXR)-induced lethal and oxidative toxicity in mice were studied. The prodrug used was d-α-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 (10-50mg/kg equivalent for d-α-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-α-tocopherol). TDMA did not significantly affect the antitumor activity of DXR in mice inoculated with L1210 leukemia cells.
公益社団法人日本薬学会の論文
1999-07-15