Ambroxol inhibits doxorubicin-induced lipid peroxidation in heart of mice

A single intravenous injection of doxorubicin (DOX, 30 mg/kg body weight) caused a significant rise in the content of lipid peroxidation products in hearts of mice. The concentration of conjugated dienes (CD) and malondialdehyde (MDA) found 24 h after injection of DOX increased about 1.8- and 2.4-fold and reached values of 11.31 +/- 2.24 A233/g and 3.72 +/- 0.40 mumol/g, respectively. The same dose of 4'-epi-doxorubicin (EPI), a less cardiotoxic epimer of DOX, increased only the heart level of MDA. Both antracyclines were not able to induce increased formation of CD in murine liver and lungs. Ambroxol, an expectorant drug which possesses the ability to scavenge hydroxyl radicals, injected intravenously (70 mg/kg) 30 min prior to DOX, completely abolished the rise in heart content of CD and MDA. The heart levels of CD and MDA in animals treated with ambroxol and DOX were 3 and 2.7 times lower than those observed in mice treated with water and DOX, respectively. Ambroxol had no effect on DOX- and EPI-induced formation of MDA in the lungs. Our results indicate that (1) DOX is a more powerful inductor lipid peroxidation in the heart than EPI; and (2) ambroxol may be useful in preventing lipid peroxidation in the heart caused by DOX.