Increased serum and cardiac acyl-carnitine/free carnitine ratio during development of doxorubicin-induced cardiotoxicity

ABSTRACT

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