Early changes in myocardial antioxidant enzymes in rats treated with adriamycin

Mol Cell Biochem. 2002 Mar;232(1-2):19-26. doi: 10.1023/a:1014862912783.


Increased oxidative stress and antioxidant deficit have been suggested to play a major role in adriamycin-induced cardiomyopathy and congestive heart failure due to multiple treatments with adriamycin (doxorubicin). In this study, we investigated the acute effects of a single dose of adriamycin on myocardial antioxidant enzymes in rats. Adriamycin (2.5 mg/kg) was injected (i.p.) and myocardial antioxidant enzyme activities, mRNA abundance and protein levels at 1, 2, 4 and 24 h were examined. While manganese superoxide dismutase (MnSOD), glutathione peroxidase (GSHPx) and catalase (CAT) activities were not significantly changed, copper-zinc superoxide dismutase (CuZnSOD) activity was reduced at all time points and this change correlated with a decrease in its protein content. CuZnSOD mRNA was increased at 1 and 24 h. GSHPx mRNA and protein levels were transiently decreased by 20 and 25% respectively at 2 h. MnSOD mRNA was not significantly changed, but its protein levels were significantly decreased at 1 h. Lipid peroxidation was increased transiently at 1, 2 and 4 h. A transient depression in antioxidant enzyme as well as transient increase in oxidative stress with a single dose of adriamycin may precede more sustained changes seen with the repeated administration of the drug and contribute to the development of cardiomyopathy and heart failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Catalase / genetics
  • Catalase / metabolism*
  • Doxorubicin / pharmacology*
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism*
  • Heart / drug effects
  • Lipid Peroxidation / drug effects
  • Male
  • Myocardium / enzymology*
  • Myocardium / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Time Factors


  • Antioxidants
  • RNA, Messenger
  • Doxorubicin
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase