Age-related Acute Adriamycin Cardiotoxicity in Mice

Abstract

Myocardial mitochondrial function after acute adriamycin exposure was compared in infant and adult mice. Heart mitochondria were isolated 48 h after an intraperitoneal injection of adriamycin. Concentrations of adriamycin in serum and heart tissue were not significantly different between infant and adult mice. Oxygen consumption (state 3 respiration), and respiratory control ratio (RCR) were studied polarographically. Enzyme activities in the respiratory chain [succinate-cytochrome c reductase (SCCR), NADH-cytochrome c reductase (NCCR), cytochrome c oxidase (CCO)], and adenine nucleotide translocase (ANT) were assayed. After saline injection (control), no significant differences were detected in state 3 respiration, RCR, and enzyme activity of ANT between infant and adult mice. The respective enzyme activities of SCCR, NCCR, and CCO in adult mice were significantly lower than those in infant mice. After adriamycin injection in adult mice, there were significant decreases in state 3 respiration (using glutamate and malate as substrates from 239 ± 25 to 160 ± 50 nanoatom O2/min/mg protein), RCR (using glutamate and malate as substrates from 7.2 ± 1.0 to 4.4 ± 1.4), and enzyme activities of SCCR (from 279 ± 30 to 178 ± 28 nmol/min/mg protein) and NCCR (from 331 ± 43 to 237 ± 30 nmol/min/mg protein), but there were no significant changes in infant mice. No significant changes in enzyme activities of CCO and ANT were found in either infant or adult mice following the administration of adriamycin. In conclusion, adriamycin is less toxic on the myocardial mitochondrial function in infant mice than in adult mice.