Effects of N-acetylcysteine, deferoxamine and selenium on doxorubicin-induced hepatotoxicity.
The aims of our study were to evaluate the antioxidant defence mechanisms of liver tissue challenged by doxorubucin (DOX) and to compare the possible protective effects of N-acetylcysteine (NAC) (n=10), deferoxamine (DOF) (n=10), DOF+NAC (n= 10) and selenium (n=9) on doxorubicin-induced hepatotoxicity. Fifty-six male rats (Mean weight = 250 ± 50 g) randomly divided into five groups. Animals in study groups were pretreated with a single dose of Dox, which was administered intravenously. Control group (n=7) was treated with intravenous saline injection. Selenium was given intraperitoneally. Blood and urine samples were collected before sacrifice. Liver tissue samples were collected and tissue superoxide dismutase (SOD), glutathione peroxidase (GSH-px), CAT activity, MDA, Zn, iron and copper were determined. DFO decreased lipid peroxidation significantly. DFO and NAC decreased CAT activity significantly. Antioxidant regimes increase SOD activities significantly. DOF and NAC increase GSH-px activities and copper levels significantly. Beneficial effect of selenium seems to result from its stimulation of SOD but not to GSH-px. It has been found that DOF, NAC and selenium have protective effects on Dox-induced hepatocellular damage. DOF+NAC did not result additional benefit.
Bulucu
Fatih
F
Department of Internal Medicine, Gulhane Military Medical Academy, Ankara, Turkey.
Ocal
Ramazan
R
Karadurmus
Nuri
N
Sahin
Mustafa
M
Kenar
Levent
L
Aydin
Ahmet
A
Oktenli
Cagatay
C
Koc
Bayram
B
Inal
Volkan
V
Yamanel
Levent
L
Yaman
Halil
H
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D004317:Doxorubicin / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
D008315:Malondialdehyde; D003300:Copper; D004317:Doxorubicin; D007501:Iron; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D012643:Selenium; D003676:Deferoxamine; D015032:Zinc; D000111:Acetylcysteine