Involvement of cardiac metallothionein in prevention of adriamycin induced lipid peroxidation in the heart.
The effect of pretreatment of mice with heavy metals: Zn, Cu, Bi, Co, Cd or Hg, against lethal and cardiac toxicity of adriamycin (ADR) was investigated. The lethal toxicity of ADR was significantly reduced by pre-administration of these metals except for Cu. The levels of both malondialdehyde and conjugated dienes, determined as indicators of lipid peroxidation in the heart, markedly increased with ADR administration, but the increases were significantly prevented by the pre-administration of Zn, Bi or Cd. The survival rate of mice after ADR injection was significantly correlated with metallothionein (MT) levels in the hearts which was increased by the injection of each metal, but was not correlated with those in the liver and kidneys. A significant negative correlation between the cardiac MT concentrations and the levels of lipid peroxidation in the hearts was also observed. These results suggest that increased MT synthesis in the heart may be involved in the protective effect of the heavy metals tested against the lethal and cardiac toxicities of ADR.
Satoh
M
M
Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Naganuma
A
A
Imura
N
N
D000818:Animals; D004317:Doxorubicin / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D006321:Heart / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000032:analysis*; D008670:Metals / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000032:analysis / Q000378:metabolism
D008670:Metals; D004317:Doxorubicin; D008668:Metallothionein