DOSE DEPENDENT CARDIAC EFFECTS OF DOXORUBICIN IN WISTAR RATS: A BIOCHEMICAL AND HISTOPATHOLOGICAL ANALYSIS

Although doxorubicin is used widely in animal models to induce cardiotoxicity, serial dose-dependent cardiac effects have not been investigated in experimental animal models to date. Therefore, the objective of this study was to find out the dose-dependent changes of doxorubicin-induced acute cardiotoxicity, both biochemically and histopathologically in Wistar rats. Wistar rats were divided into nine groups. Group 1: normal control; Groups 2-9: eight doses of doxorubicin (13, 14, 15, 16, 17, 18, 19 & 20 mg/kg, intraperitoneal injection, after 16 h fast). Animals were sacrificed on the 4^th day, and blood was collected for the estimation of cardiac troponin I (cTnI), aspartate aminotransferase (AST) and superoxide dismutase (SOD) activities and heart tissues were collected for histopathological assessment. Mean cTnI concentrations of groups 1-9 were 0, 39.46 ± 1.8, 60.92 ± 2.7, 87.79 ± 1.8, 116.96 ± 2.7, 147.79 ± 2.3, 163.96 ± 1.5, 197.38 ± 2.3 and 221.54 ± 1.8 pg/mL respectively. In groups 1-9, mean AST activities were 38.90 ± 0.98, 42.23 ± 0.99, 44.07 ± 1.20, 50.77 ± 1.70, 57.93 ± 3.40, 58.54 ± 0.65, 63.57 ± 0.69, 68.94 ± 2.20 and 79.83 ± 1.20 U/L and SOD activities were 77.73 ± 0.86, 72.92 ± 1.3, 66.49 ± 0.91, 54.06 ± 0.92, 28.01 ± 0.45, 21.12 ± 0.56, 16.12 ± 0.46, 14.34 ± 0.70 and 8.75 ± 0.94% respectively. Significant differences (P<0.05) between group 1 and groups 2-9 were evident in all three diagnostic parameters. Degree of histopathological damage due to doxorubicin increased with increasing dosage of doxorubicin.