Activity of antioxidative enzymes in erythrocytes after a single dose administration of doxorubicin in rats pretreated with fullerenol C(60)(OH)(24).
In earlier in vitro investigations, fullerenol was shown to have a strong antioxidative capability. The present study examined the role of fullerenol as a potential antioxidative protector for doxorubicin-induced oxidative stress in the blood of rats through an investigation of the activity of glutathione-dependent enzymes (glutathione-S-transferase and glutathione peroxidase). It also assessed the influence of fullerenol on the number of blood cells (leukocytes and erythrocytes) as well as on the content of hemoglobin after a single dose administration of doxorubicin. Experiments were performed on six groups of adult male Wistar rats, each group containing eight individuals. Doxorubicin was administrated i.v. (tail vein) in a single dose of 10 mg/kg. Fullerenol C(60)(OH)(24) was administrated to the treated animals i.p. (in doses 50, 100, 200 mg/kg) 30 min before the dosing with doxorubicin. The control group animals were given saline (1 ml/kg; i.p.). One group of animals was treated only with fullerenol (100 mg/kg i.p.). The animals were sacrificed 2 and 14 days after the treatment. Each experiment was repeated twice. The results may indicate that fullerenol induces a decrease in the antioxidative capacity of erythrocytes in oxidative stress conditions, whereas, without doxorubicin, the application of fullerenol did not induce any changes in the enzyme activity of erythrocytes. The results of GST activity might indicate that 50 mg/kg are not sufficient to protect from doxorubicin toxicity, while 200 mg/kg might be toxic for animals, judging from the increase in GST activity.
Milic
Vukosava Djordjevic
VD
Medical Faculty, Department of Pharmacy, University of Novi Sad, Novi Sad, Serbia.
Stankov
Karmen
K
Injac
Rade
R
Djordjevic
Aleksandar
A
Srdjenovic
Branislava
B
Govedarica
Biljana
B
Radic
Natasa
N
Simic
Viktorija Dragojevic
VD
Strukelj
Borut
B
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D037741:Fullerenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D037741:Fullerenes; C408042:fullerol C60(OH)24; D004317:Doxorubicin; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase