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Doxorubicin (Dox) is an anthracycline used to treat various malignancies and is a potent inducer of cardiac injury. N-Acetyl-L-cysteine (NAC) is used as a mucolytic and an antioxidant and is a precursor of glutathione, an intracellular antioxidant and a scavenger of hydrogen peroxide. The aim of our study was to determine whether NAC could prevent myocardial injury induced by Dox, whether NAC can attenuate the cytotoxicity of Dox on cultured lymphocytes and whether NAC could prevent lymphocyte apoptosis. Using cultured human peripheral lymphocytes, in vitro experiments were carried out to investigate the effects of NAC on lymphocyte viability, apoptosis and glutathione content. To mimic the therapeutic condition of anthracycline treatment, we used a clinically relevant concentration (10 microM) of Dox. The viability of cultured lymphocytes decreased by nearly 25% after 48 h culture with 10 microM of Dox and by more than 65% when treated for 72 h. The percentage of apoptotic lymphocytes in the Dox group was nearly 12 times that of the controls. NAC could inhibit apoptosis of cultured lymphocytes by 50% in the presence of 10 microM Dox. There was no difference of intracellular glutathione level between Dox and NAC+Dox groups. Our results demonstrated that NAC was able to inhibit the apoptosis of lymphocytes, but it could not prevent myocardial injury induced by Dox. Further clinical studies of the combination of NAC and Dox will be needed to determine
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