Chemico-Biological Interactions 127 (2000) 1–11
Basal and drug-induced antioxidant enzyme
activities correlate with age-dependent
doxorubicin oxidative toxicity
Chris A. Pritsos *, J. Ma
Centre for En6ironmental Science and Engineering, Uni6ersity of Ne6ada, Mail Stop
Received 24 August 1999; received in revised form 14 February 2000; accepted 18 February 2000
Doxorubicin continues to be one of the most widely used anticancer agents in the clinic
despite its dose-limiting side-effects. Many of doxorubicin’s dose-limiting toxicities occur due
to its generation of toxic oxygen species, resulting in oxidative stress. Some clinical
observations have suggested that doxorubicin may have greater toxicity in older patients.
The studies presented here compare basal and doxorubicin-induced antioxidant enzyme
activities in brain, heart, kidney and liver tissues of Fisher 344 rats of different ages to
determine whether differences in these enzymes can account for the age-dependent differ-
ences observed in doxorubicin-induced toxicity. Three groups of animals were tested, young
animals (2-months-old), adult animals (10-months-old) and old animals (18-months-old).
The results of these studies show that in general young and adult animals have similar levels
of antioxidant enzyme activity while the older animals have less. Only in the young animals
is antioxidant enzyme activity signiﬁcantly increased following doxorubicin treatment sug-
gesting that enzyme induction occurs only in the young group of animals. Lipid peroxidation
is shown to have the greatest increase in the old animals following doxorubicin treatment
while the young animals have the smallest increase. The results from these studies suggest
that there is an increase in doxorubicin-induced oxidative damage with age and that these
differences may be due to basal and drug-induced differences in tissue antioxidant enzyme
activities. © 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.
Age; Anthracyclines; Antioxidant enzymes; Doxorubicin; Lipid peroxidation; Oxidative stress
* Corresponding author. Tel.: + 1-775-3275096; fax: +1-775-3275051.
0009-2797/00/$ - see front matter © 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.