N-acetylcysteine amide decreases oxidative stress but not cell death induced by doxorubicin in H9c2 cardiomyocytes
While doxorubicin (DOX) is widely used in cancer chemotherapy, long-term severe cardiotoxicity limits its use. This is the first report of the chemoprotective efficacy of a relatively new thiol antioxidant, N-acetylcysteine amide (NACA), on DOX-induced cell death in cardiomyocytes.
We hypothesized that NACA would protect H9c2 cardiomyocytes from DOX-induced toxicity by reducing oxidative stress. Accordingly, we determined the ability of NACA to mitigate the cytotoxicity of DOX in H9c2 cells and correlated these effects with the production of indicators of oxidative stress.
Results: DOX (5 uM) induced cardiotoxicity while 1) increasing the generation of reactive oxygen species (ROS), 2) decreasing levels and activities of antioxidants and antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase) and 3) increasing lipid peroxidation. NACA substantially reduced the levels of ROS of the degree of lipid peroxidation products, and increases in both GSH level and GSH/GSSG ratio.
However, treating H9c2 cells with NACA (750 uM) did little to protect H9c2 cells from DOX-induced cell death.
Conclusions: NACA did little to protect NACA H9c2 cells from DOX-induced cell death, even though NACA mitigated the DOX induced decrease of the activities of all of the antioxidant enzymes.
These unexpected results suggest that mechanisms not dependent on the production of ROS are involved in DOX induced apoptosis in cardiomyocytes.
Author: Rong Shi, Chuan-Chin Huang, Robert S Aronstam, Nuran Ercal, Adam Martin and Yue-wern Huang
Credits/Source: BMC Pharmacology 2009, 9:7
Published on: 2009-04-15
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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