Lipid peroxidation of rat myocardial tissue following daunomycin administration.
Daunomycin-induced cardiotoxicity has been regarded to be the result of oxygen-mediated lipid peroxidation of cell membranes. The aim of the present work was to evaluate the extent of lipid peroxidation in rat heart after administration of this anticancer drug and, further, to examine possible activation of some endogenous antioxidant defense systems. Myocardial tissue from both control and drug-treated rats was tested for lipid peroxidation using a selective third-order derivative method that is based on the analysis of the free malondialdehyde produced. Determination of reduced/oxidized glutathione levels and measurement of the activity of DT-diaphorase, glutathione-S-transferase, glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-cytochrome P-450 reductase were also carried out using literature methods. Significant increase of malondialdehyde content, and DT-diaphorase and glutathione-S-transferase activities were found in myocardial tissue from daunomycin-treated rats. On the other hand, reduced and oxidized glutathione levels were significantly decreased while the activity of glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-cytochrome P-450 reductase remained unchanged after daunomycin administration. The results of the present study give further evidence that daunomycin can induce lipid peroxidation in heart. However, additional experimentation is needed in order to delineate the molecular details of this process as well as of the mechanisms evolved to limit it.
Papageorgiou
G
G
Laboratory of Biological Chemistry, School of Medicine, Aristotle University, Thessaloniki, Greece.
Iliadis
S
S
Botsoglou
N
N
Dioudis
C
C
Goulas
A
A
Fletouris
D
D
Dimitriadou-Vafiadou
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D003630:Daunorubicin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D015227:Lipid Peroxidation; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D003630:Daunorubicin