Glutamine protects against doxorubicin-induced cardiotoxicity.
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).


CONCLUSIONS
These data suggest that dietary GLN supplementation may diminish DOX-induced oxidative damage and thus cardiotoxicity through upregulation of cardiac GSH metabolism.
Cao
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Y
Department of Pharmacology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
Kennedy
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R
Klimberg
V S
VS
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000517:prevention & control*; D004317:Doxorubicin; D004435:Eating / Q000187:drug effects; D005260:Female; D005973:Glutamine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D008054:Lipid Peroxides; D005973:Glutamine; D004317:Doxorubicin; D005978:Glutathione