Purpose:
Previous studies have shown catabolism of adenosine 5’-triphosphate (ATP) in systemic blood is a
potential surrogate biomarker for cardiovascular toxicity. We compared the acute toxicity of high doses of doxorubicin
(DOX) and isoproterenol (ISO) on hemodynamics and ATP catabolism in systemic circulation.
Methods:
Sprague Dawley (SD) rats (n = 8 – 11) were each given either a single dose of 30 mg/kg ISO, or twice-daily
dose of 10 mg/kg of DOX or normal saline (control) for 4 doses by subcutaneous injection. Blood samples were collected
up to 6 hours for measuring concentrations of ATP and its catabolites. Hemodynmics was recorded continuously.
Difference was considered significant at p < 0.05 (ANOVA).
Results and Discussion:
Mortality was 1/8, 5/11 and 0/11 for the DOX, ISO and control groups, respectively. Systolic
blood pressure was significantly lower in the DOX and ISO treated rats than in the control measured at the last recorded
time (76 ± 9 for DOX vs 42 ± 8 for ISO vs 103 ± 5 mmHg for Control, p < 0.05 for all). Blood pressure fell gradually
after the final injection for both DOX and control groups, but abruptly after ISO followed by a rebound and then gradual
decline till the end of the experiment. Heart rate was significantly higher after ISO, but no difference between the DOX
and control rats (p > 0.05). RBC concentrations of ADP and AMP, and plasma concentrations of adenosine and uric acid
were significantly higher in the ISO group. In contrast, hypoxanthine concentrations were significantly higher in the DOX
treated group (p < 0.05).
Conclusion:
Acute cardiovascular toxicity induced by DOX and ISO may be measured by changes in hemodynamics and
breakdown of ATP and adenosine in the systemic circulation, albeit a notable qualitative and quantitative difference was
observed.