Effects of N-Acetylcysteine, Deferoxamine and Selenium on Doxorubicin-Induced Hepatotoxicity

被引:39
作者
Bulucu, Fatih [2 ]
Ocal, Ramazan [2 ]
Karadurmus, Nuri [2 ]
Sahin, Mustafa [1 ]
Kenar, Levent [3 ]
Aydin, Ahmet [4 ]
Oktenli, Cagatay [2 ]
Koc, Bayram [2 ]
Inal, Volkan [5 ]
Yamanel, Levent [6 ]
Yaman, Halil [3 ]
机构
[1] Gulhane Mil Med Acad, Dept Endocrinol, Ankara, Turkey
[2] Gulhane Mil Med Acad, Dept Internal Med, Ankara, Turkey
[3] Gulhane Mil Med Acad, Dept Biochem & Clin Biochem, Ankara, Turkey
[4] Gulhane Mil Med Acad, Dept Pharmaceut Sci, Ankara, Turkey
[5] Mil Hosp, Dept Internal Med, Eskisehir, Turkey
[6] Gulhane Mil Med Acad, Dept Intens Care Med, Ankara, Turkey
关键词
Doxorubicin hepatotoxicity; Deferoxamine; N-acetylcysteine; Selenium; Rat; OXIDATIVE STRESS; PROTECTIVE ROLE; VITAMIN-E; MEDIATED TOXICITY; LUNG INJURY; ADRIAMYCIN; RATS; METABOLITES; CADMIUM; DAMAGE;
D O I
10.1007/s12011-009-8377-y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:184 / 196
页数:13
相关论文
共 42 条
[1]
AEBI H, 1984, METHOD ENZYMOL, V105, P121
[2]
N-acetyl L-cysteine attenuates oxidant-mediated toxicity induced by chrysotile fibers [J].
Afaq, F ;
Abidi, P ;
Rahman, Q .
TOXICOLOGY LETTERS, 2000, 117 (1-2) :53-60
[3]
The effect of n-acetylcysteine and deferoxamine on exercise-induced oxidative damage in striatum and hippocampus of mice [J].
Aguiar, Aderbal S., Jr. ;
Tuon, Talita ;
Soares, Fernanda S. ;
C. da Rocha, Luis Gustavo ;
Silveira, Paulo Cesar ;
Pinho, Ricardo A. .
NEUROCHEMICAL RESEARCH, 2008, 33 (05) :729-736
[4]
N-Acetylcysteine -: a safe antidote for cysteine/glutathione deficiency [J].
Atkuri, Kondala R. ;
Mantovani, John J. ;
Herzenberg, Leonard A. ;
Herzenberg, Leonore A. .
CURRENT OPINION IN PHARMACOLOGY, 2007, 7 (04) :355-359
[5]
Oxidative stress and nitric oxide related parameters in type II diabetes mellitus:: effects of glycemic control [J].
Aydin, A ;
Orhan, H ;
Sayal, A ;
Özata, M ;
Sahin, G ;
Isimer, A .
CLINICAL BIOCHEMISTRY, 2001, 34 (01) :65-70
[6]
PROTECTIVE ROLE OF THE GLUTATHIONE REDOX CYCLE AGAINST ADRIAMYCIN-MEDIATED TOXICITY IN ISOLATED HEPATOCYTES [J].
BABSON, JR ;
ABELL, NS ;
REED, DJ .
BIOCHEMICAL PHARMACOLOGY, 1981, 30 (16) :2299-2304
[7]
ADRIAMYCIN-INDUCED HEPATIC AND MYOCARDIAL LIPID-PEROXIDATION AND DNA-DAMAGE, AND ENHANCED EXCRETION OF URINARY LIPID METABOLITES IN RATS [J].
BAGCHI, D ;
BAGCHI, M ;
HASSOUN, EA ;
KELLY, J ;
STOHS, SJ .
TOXICOLOGY, 1995, 95 (1-3) :1-9
[8]
Detrimental effects of N-acetylcysteine plus desferoxamine combination in an experimental nephrotic syndrome model [J].
Bulucu, F. ;
Oktenli, C. ;
Kenar, L. ;
Koc, B. ;
Ocal, R. ;
Karadurmus, N. ;
Inal, V. ;
Yamanel, L. ;
Sanisoglu, Y. S. ;
Aydin, A. .
INTERNATIONAL JOURNAL OF TOXICOLOGY, 2007, 26 (06) :525-532
[9]
Bulucu F, 2008, J NEPHROL, V21, P576
[10]
Doxorubicin and mechanical performance of cardiac trabeculae after acute and chronic treatment: a review [J].
De Beer, EL ;
Bottone, AE ;
Voest, EE .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2001, 415 (01) :1-11