Doxorubicin (DOX) dose-intensive therapy for breast cancer is limited by a cardiomyopathy that often results in overt congestive heart failure. We hypothesized that dietary glutamine (GLN) can diminish DOX-induced cardiotoxicity by maintaining tissue glutathione (GSH) levels and thus preventing the proposed mechanism of cardiac injury: oxidation.
Methods: Forty-two female Fisher 344 rats were randomized into one of six groups: GLN + saline (SAL), GLN + DOX, freamine (FA) + SAL, FA + DOX, H2O + SAL, and H2O + DOX. Rats were pair-fed chow and gavaged with 1 g/kg/day GLN or an isonitrogenous amount of FA or H2O for 28 days. Rats were injected intravenously with a single dose of SAL or 9 mg/kg DOX on day 7 of gavage. At 28 days (21 days post-DOX), rats were sacrificed and blood and cardiac tissue were assayed for GLN and GSH content and lipid peroxidation (LP).
Results: There were no differences in cardiac GSH levels and cardiac lipid peroxidation in GLN + SAL versus GLN + DOX groups. However, blood and cardiac GSH levels were significantly decreased in H2O + DOX and FA + DOX groups compared to controls (H2O + SAL and FA + SAL).
Conclusion: These data suggest that dietary GLN supplementation may diminish DOX-induced oxidative damage and thus cardiotoxicity through upregulation of cardiac GSH metabolism.
Copyright 1999 Academic Press.