The investigation of the effects of acetyl l-carnitine on experimental doxorubicin-induced cardiotoxicity

Objective: Anthracyclines are one of the most preferred agents on childhood malignancies. However they have dose limited side effects such as cardiotoxicity. On this study it was aimed to reveal by echocardiogram and ultrastructural studies, if ALCAR (acetyl-L-carnitine), which aims oxidative stresses and the mechanism that create oxygen radicals, has a preventive affect on Doxorubicine cardiotoxicity.Materials and method: : In this study, 28 Wistar albino male rats weighing 180-220 g were divided into four groups as control, Doxorubicine, ALCAR, ALCAR+Doxorubicine. Rats in the first group were given saline day 1-10; the second group were given a single dose of Doxorubicin (15mg/kg/doz) on the fifth day but saline on the other days; the third group were given ALCAR day 1-10(300mg/kg/doz), and the fourth group were given ALCAR day 1-10(300mg/kg/doz) but given a single dose of Doxorubicin (15mg/kg/doz) on the fifth day of the study. To evaluate the cardiac functions, ejection fractions (EF) were measured by echocardiography before and after Doxorubisin application. H&E (hematoxylin and eosin) and Masson trichrome applications and electron microscobic examinations to expose the structural changes. TUNEL and caspas-3 immunohistochemical applications were performed to show apoptosis. Results: Examining the echocardiography results; Doxorubicine application is found to decrease the EF values and this result is statistically significant, ALCAR application only is found to increase the EF values contrarily.ALCAR application before Doxorubicine is found to prevent the cardiac injury and the EF fall that Doxorubicine causes ; the EF values remain on the initial levels. The histopathologically and electron microscopical examinations indicate that the Doxorubicine application causes cardiac injury not only functionally but also structurally, pre and post Doxorubicin application of ALCAR is found to prevent this injury. In this study apoptosis; which is pointed as an important mechanism of Doxorubicine toxicity is evaluated by TUNEL and caspas-3 immunohistochemical procedures. Both TUNEL and caspas-3 procedures indicate that Doxorubicine induces apoptosis significantly and causes cardiac cell death, pre and postapplication of ALCAR is found to decrease that affect and the results were 4statistically significant. ALCAR application is found to reduce the apoptosis that Doxorubicine causes but the affect was not enough to decrease the levels to control group values. Conclusion: The cardiotoxicity that Doxorubicine causes is an important problem that is usually faced on practical pediatric oncology. The results of our study represent that Pre and post application of ALCAR seems to be able to prevent the cardiac injury that Doxorubicine causes in both functional and structural ways, and to be able to reduce the side affects of Doxorubicine or to clear them all away