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 |
|---|---|
| Pages (from-to) | 698-702 |
| Number of pages | 5 |
| Journal | Biological and Pharmaceutical Bulletin |
| Volume | 22 |
| Issue number | 7 |
| Publication status | Published - 1999 Jul |
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Keywords
- D-α-tocopheryl N,N-dimethylaminoacetate
- Doxorubicin
- Lipid peroxidation
- Oxidative stress
- Vitamin E
- Water soluble prodrug
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology, Toxicology and Pharmaceutics(all)
Cite this
Effects of a water-soluble prodrug of vitamin E on doxorubicin-induced toxicity in mice. / Itoh, Yoshiko; Takata, Jiro; Yoshiharu Karube, A.; Matsushima, Yoshikazu.
In: Biological and Pharmaceutical Bulletin, Vol. 22, No. 7, 07.1999, p. 698-702.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of a water-soluble prodrug of vitamin E on doxorubicin-induced toxicity in mice
AU - Itoh, Yoshiko
AU - Takata, Jiro
AU - Yoshiharu Karube, A.
AU - Matsushima, Yoshikazu
PY - 1999/7
Y1 - 1999/7
N2 - 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.
AB - 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.
KW - D-α-tocopheryl N,N-dimethylaminoacetate
KW - Doxorubicin
KW - Lipid peroxidation
KW - Oxidative stress
KW - Vitamin E
KW - Water soluble prodrug
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UR - http://www.scopus.com/inward/citedby.url?scp=0032802531&partnerID=8YFLogxK
M3 - Article
C2 - 10443465
AN - SCOPUS:0032802531
VL - 22
SP - 698
EP - 702
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
SN - 0918-6158
IS - 7
ER -