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Vol. 288, Issue 3, 938-944, March 1999
Department of Medicine, University of Louisville School of
Medicine, Louisville, Kentucky
Controversial results have been reported regarding whether
metallothionein (MT) functions in doxorubicin (DOX) detoxification in
the heart. To determine unequivocally the role of MT in cardiac protection against the toxicity of DOX, ventricular cardiomyocytes isolated from 1- to 3-day neonatal transgenic mice with high levels of
cardiac MT and from nontransgenic control animals were applied. On the
6th day of culturing, MT concentrations in the transgenic cardiomyocytes were about 2-fold higher than those in the nontransgenic cells. DOX was added directly into the cultures. Compared with nontransgenic controls, transgenic cardiomyocytes displayed a significant (p < .05) resistance to DOX
cytotoxicity, as measured by morphological alterations, cell viability,
and lactate dehydrogenase leakage from the cells. This cytoprotective
effect of MT correlated with its inhibition of DOX-induced lipid
peroxidation. These observations demonstrate unequivocally that
elevation of MT concentrations in the cardiomyocytes of 2-fold higher
than normal provides efficient protection against DOX toxicity.
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