BACKGROUND & OBJECTIVE: Herceptin is a humanized monoclonal antibody for 
treating the patients with metastatic breast cancers overexpressing human 
epidermal growth factor receptor (HER-2). Herceptin combined with doxorubicin 
markedly increased the incidence of cardiac dysfunction in clinical trials. The 
current study was designed to investigate the cardiotoxicity aggravated by 
Herceptin combined with doxorubicin in rats.
METHODS: Thirty-six female rats were randomized into four groups (n=9): control 
group, Herceptin group, doxorubicin group, Herceptin combined with doxorubicin 
group. The value of malon dialdehyde (MDA) was measured by thiobarbituric acid 
(TBA) method and the activity of glutathione peroxidase (GSH-Px) was measured by 
5,5'-dithiobis-2-nitrobenzoic acid (DTNB) method. The damage and apoptosis of 
myocardium were observed by electron microscopy and tdt-mediated dUTP nick end 
labeling (TUNEL). The ratio of myocardial apoptosis cells was quantified using 
flow cytometry.
RESULTS: The value of MDA in control group and Herceptin group were 
(0.70+/-0.03) and (0.73+/-0.05) nmol x(mg x protein)(-1), respectively; the 
activity of GSH-PX in control group and Herceptin group were (81.31+/-0.13) and 
(78.43+/-0.15) U x(mg x protein)(-1),respectively;the two groups were similar. 
The value of MDA in doxorubicin group and Herceptin combined with doxorubicin 
group were (0.88+/-0.10) and (0.94+/-0.13) nmol x(mg x protein)(-1), 
respectively; the activity of GSH-PX in doxorubicin group and Herceptin combined 
with doxorubicin group were(67.88+/-0.24) and(63.37+/-0.28) U x(mg x 
protein)(-1),respectively. The most prominent ultrastructural damages were 
mitochondrial swelling with fragmentation of cristae and vacuoles formation in 
doxorubicin group and Herceptin combined with doxorubicin group. Herceptin 
markedly increased the ratio of apoptosis of myocardial cells from (5.35+/-0.27) 
% in doxorubicin group to (8.27+/-0.38) % in Herceptin combined with doxorubicin 
group as measured by flow cytometry (P< 0.05).
CONCLUSION: Herceptin alone had little toxic effects on rat cardiomocytes, but 
Herceptin combined with doxorubicin can aggravate rat cardiotoxicity. Herceptin 
can also increase the number of the apoptosis cell in rat myocardium.