Post-treatment with ambroxol and N-acetylcysteine reduces the doxorubicin-induced oxidative stress in hearts and lungs of mice

Introduction: Ambroxol and N-acetylcysteine are widely used mucolytic drugs that have antioxidant properties. We tested whether these drugs at the iv. dose of 0.169 mmoles/kg of body weight can inhibit the doxorubicin (DOX)-induced oxidative stress in murine heart and lungs. Material and Methods: Mice (n=10 in each group) were injected iv. with DOX (30 mg/kg) or 0.9% NaCl and then after 30 min with ambroxol, N-acetylcysteine, the combination of both drugs, or 0.9% NaCl. At 5th h from DOX injection the concentration of thiobarbituric acid reactive substances (TBARs) and Schiff bases (SB)- two end-products of lipidperoxidation, and the activity of H2O2 were determined in heart and lung homogenates. Results: Ambroxol and N-acetylcysteine significantly attenuated the DOX-elicited rise in the end-products of lipid peroxidation and H2O2 activity in hearts and lungs. Post-treatment with the combination of ambroxol and N-acetylcysteine was the most effective on inhibition of DOX-induced TBARs and H2O2 generation in heart homogenates. The heart levels of TBARs and H2O2 decreased from 2.73±0.15 μM/g and 6.02±0.41 μM in mice injected with DOX and 0.9% NaCl to 1.55±0.09 μM/g and 0.57± 0.04 μM in animals treated with DOX and ambroxol plus N-acetylcysteine (p<0.05), respectively. However, the inhibitory effect on DOX-evoked SB formation in hearts and lungs was similar for all antioxidant treatments. Conclusions: These indicate that ambroxoland N-acetylcysteine can inhibitoxidative stress in mice treated with single injection of DOX. Combination of ambroxol and N-acetylcysteine seems to be a possible candidate for prevention of the anthracycline-induced cardiotoxicity. (Clin. Exp. Med. Lett. 2006; 47(3):161-167)

Keywords: Ambroxol, N-acetylcysteine, heart injury