Lipid peroxidation and antioxidant defense mechanisms in rat renal tissue after daunorubicin administration.
Redox cycling compounds such as daunorubicin have been assumed to be toxic because they stimulate reactive oxygen-mediated lipid peroxidation. Furthermore, both DT-diaphorase and glutathione (GSH) have been regarded as protective cellular compounds against daunorubicin cardiotoxicity, but their role in daunorubicin nephrotoxicity remains unclear. To investigate this issue, 10 adult Wistar rats were twice injected with a single dose of 20 mg/kg body weight daunorubicin into the tail vein; the interval between injections was 48 h. A control group of 10 rats were injected with normal saline. One day after the second injection, all the animals were sacrificed and their kidneys were analyzed for malondialdehyde (MDA) as an index of lipid peroxidation, DT-diaphorase activity, and GSH and glutathione disulphide (GSSG) content. A significant increase of MDA concentration (2.41 vs. 1.64 p < 0.001) and DT-diaphorase activity (0.2 vs. 0.12, p < 0.001) was found in the renal tissue of daunorubicin injected rats. In contrast, GSH and GSSG levels were decreased in those animals (566 vs. 1282, p < 0.001 and 115 vs 187, p < 0.01, respectively). The results of this study give evidence that a high dosage of daunorubicin induces lipid peroxidation in renal tissue of rats stimulating the activation of DT-diaphorase and the detoxificative depletion of GSH.
Dioudis
C
C
First Medical Department, School of Medicine, Aristotle University Thessaloniki, Greece.
Grekas
D
D
Papageorgiou
G
G
Iliadis
S
S
Botsoglou
N
N
Zilidis
C
C
Tourkantonis
A
A
Trakatellis
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers; D003630:Daunorubicin / Q000633:toxicity*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D015415:Biomarkers; D008315:Malondialdehyde; D016660:NAD(P)H Dehydrogenase (Quinone); D005978:Glutathione; D019803:Glutathione Disulfide; D003630:Daunorubicin