Effect of Quercetin on Daunorubicin-Induced Heart Mitochondria Changes in Rats

J. GUZY, J. KUŠNÍR, M. MAREKOVÁ, Z. CHAVKOVÁ, K. DUBAYOVÁ,
G. MOJŽIŠOVÁ¹, L. MIROSSAY², J. MOJŽIŠ²

Department of Medical Chemistry and Biochemistry, ¹Department of Experimental Medicine and ²Department of Pharmacology, Medical Faculty, Šafarik University, Košice, Slovak Republic

Received December 12, 2002
Accepted April 8, 2003

Summary
Cancer therapy with daunorubicin is limited by its cardiotoxicity. It has been suggested that daunorubicin-induced free radical generation can be involved. The precise molecular mechanism of daunorubicin-induced cardiotoxicity is still not well understood but it is believed that mitochondria play an important role in this process. It has been reported that flavonoids with antioxidant properties may prevent anthracycline-induced cardiotoxicity. In this work, we investigated the effects of daunorubicin and quercetin on mitochondrial enzyme activities such as ATPase, glutathione peroxidase (GPx) and glutathione reductase (GR). Moreover, we also studied the changes of outer mitochondrial membrane using synchronous fluorescence spectra. The actitivity of ATPase and GR were significantly increased after daunorubicin application. Pretreatment with quercetin significantly alleviated this increase. On the other hand, GPx activity was significantly decreased and quercetin prevented this decrease. Treatment with quercetin alone had no significant effect on the enzyme activity studied. Quercetin also completely prevented daunorubicin-induced changes in fluorescence of the outer mitochondrial membrane. In conclusion, our data indicate that quercetin may be useful in mitigating daunorubicin-induced cardiotoxicity.

Key words
Mitochondria • Antioxidant enzymes • Daunorubicin • Quercetin • Synchronous fluorescence spectra