AMBROXOL INHIBITS DOXORUBICIN-INDUCED LIPID-PEROXIDATION IN HEART OF MICE

A single intravenous injection of doxorubicin (DOX, 30 mg/kg body weig ht) caused a significant rise in the content of lipid peroxidation pro ducts in hearts of mice. The concentration of conjugated dienes (CD) a nd malondialdehyde (MDA) found 24 h after injection of DOX increased a bout 1.8- and 2.4-fold and reached values of 11.31 +/- 2.24 A(233)/g a nd 3.72 +/- 0.40 mu mol/g, respectively. The same dose of 4'-epi-doxor ubicin (EPI), a less cardiotoxic epimer of DOX, increased only the hea rt level of MDA. Both antracyclines were not able to induce increased formation of CD in murine liver and lungs, Ambroxol, an expectorant dr ug which possesses the ability to Scavenge hydroxyl radicals, injected intravenously (70 mg/kg) 30 min prior to DOX, completely abolished th e 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 th an those observed in mice treated with water and DOX, respectively. Am broxol had no effect on DOX- and EPI-induced formation of MDA in the l ungs. Our results indicate that (1) DOX is a more powerful inductor li pid peroxidation in the heart than EPI; and (2) ambroxol may be useful in preventing lipid peroxidation in the heart caused by DOX.