Tamoxifen inhibits lipid peroxidation in cardiac microsomes. Comparison with liver microsomes and potential relevance to the cardiovascular benefits associated with cancer prevention and treatment by tamoxifen.
Tamoxifen and 4-hydroxytamoxifen were both good inhibitors of iron-dependent lipid peroxidation in rat cardiac microsomes. Tamoxifen was also a good inhibitor of lipid peroxidation in liposomes prepared from the phospholipid obtained from rat liver microsomes. In a modified rat liver microsomal system containing a sufficiently low amount of peroxidizable phospholipid to make it comparable with the rat cardiac microsomal system, tamoxifen and 4-hydroxytamoxifen were of similar effectiveness as in the cardiac system. Tamoxifen is known to lower serum cholesterol levels, and the findings reported here indicate that the drug might also protect heart cell membranes against peroxidative damage. Potential cardioprotective and antiatherosclerotic benefits of tamoxifen are discussed in relation to the drug's use in cancer prevention and treatment.
Biomedical Sciences Division, King's College London, Strand, U.K.
H
H
Wiseman
M
M
Cannon
H R
HR
Arnstein
B
B
Halliwell
D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D007501:Iron / Q000037:antagonists & inhibitors; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes; D008297:Male; D008861:Microsomes / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000517:prevention & control*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D008081:Liposomes; D010743:Phospholipids; D017392:Thiobarbituric Acid Reactive Substances; D013629:Tamoxifen; C016601:afimoxifene; D007501:Iron