Abstract
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-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 - 50 mg/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.
Original language | English |
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Pages (from-to) | 698-702 |
Number of pages | 5 |
Journal | Biological and Pharmaceutical Bulletin |
Volume | 22 |
Issue number | 7 |
DOIs | |
Publication status | Published - 1999 Jul |
Keywords
- D-α-tocopheryl N,N-dimethylaminoacetate
- Doxorubicin
- Lipid peroxidation
- Oxidative stress
- Vitamin E
- Water soluble prodrug
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science