INCREASED SERUM AND CARDIAC ACYL-CARNITINE/FREE CARNITINE RATIO DURING DEVELOPMENT OF DOXORUBICIN-INDUCED CARDIOTOXICITY

This study has been initiated to investigate whether cumulative doxorubicin (DOX) therapy alters serum and cardiac carnitine levels and if so, whether these alterations should be viewed as a mechanism and/or as an index during development of DOX-induced cardiotoxicity. To achieve the ultimate goal of this study, a total of 40 adult male Wistar albino rats were divided into 4 groups. In the first group, animals were injected intraperitoneally (I.P.) with normal saline (0.5 ml/200 gm body weight) and served as a normal control. Animals in the second to the fourth groups were injected every other day with DOX (3 mg/kg, I.P.), to obtain treatments with cumulative doses of 6 mg/kg (group 2), 12 mg/kg (group 3) and 18 mg/kg (group 4). At 24 hours after receiving the last dose of DOX, animals were sacrificed, serum as well as hearts were isolated and analyzed. DOX induced a significant and dose-dependent increase in serum creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), acyl-carnitine (AC)/free carnitine (FC) ratio and a significant decrease in serum free FC. In cardiac tissues, DOX induced a significant 46 % and 63 % decrease in FC after cumulative doses of 12 and 18 mg/kg, respectively. In contrast to FC, DOX induced a significant 70 % and 81 % increase in AC after cumulative doses of 12 and 18 mg/kg, respectively. Moreover, DOX treatment showed significant and dose-dependent decrease in adenosine triphosphate (ATP) level in cardiac tissues. In conclusion, data from this study suggest that: (1) Decreased myocardial carnitine level should be viewed as a mechanism during development of DOX cardiotoxicity, and (2) the parallel increase of serum AC/FC ratio and cardiotoxicity enzymatic indices, may point to the possible consideration of AC/FC ratio as a marker during development of DOX cardiotoxicity.