Melatonin Enhances Tamoxifen's Ability to Prevent the Reduction in Microsomal Membrane Fluidity Induced by Lipid Peroxidation |
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Authors: | JJ García RJ Reiter GG Ortiz CS Oh L Tang BP Yu G Escames |
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Institution: | (1) Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284, USA, US;(2) Department of Physiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284, USA, US |
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Abstract: | The indoleamine melatonin and the synthetic antiestrogenic drug tamoxifen seem to have similar mechanisms in inhibiting the
growth of estrogen receptor positive breast cancer cells. In this study, we compared the ability of these molecules, alone
and in combination, in stabilizing microsomal membranes against free radical attack. Hepatic microsomes were obtained from
male rats and incubated with or without tamoxifen (50–200 μm), melatonin (1 mm) or both; lipid peroxidation was induced by addition of FeCl3, NADPH and ADP. After oxidative damage, membrane fluidity, measured by fluorescence polarization techniques, decreased whereas
malonaldehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations increased. Incubation of the microsomes with tamoxifen prior
to exposure to free radical generating processes inhibited, in a dose-dependent manner, the increase in membrane rigidity
and the rise in MDA+4-HDA levels. When melatonin was added, the efficacy of tamoxifen in preventing membrane rigidity was
enhanced. Thus, the IC50s for preventing membrane rigidity and for inhibiting lipid peroxidation obtained for tamoxifen in the presence of melatonin
were lower than those obtained with tamoxifen alone. Moreover, tamoxifen (50–200 μm) in the presence of melatonin reduced basal membrane fluidity and MDA+4-HDA levels in microsomes. These synergistic effects
of tamoxifen and melatonin in stabilizing biological membranes may be important in protecting membranes from free radical
damage.
Received: 7 July 1997/Revised: 12 November 1997 |
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Keywords: | : Melatonin — Tamoxifen — Antioxidant — Lipid peroxidation — Membrane fluidity — Microsome |
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