Attenuation of cyclophosphamide induced toxicity by squalene in experimental rats

被引:72
作者
Senthilkumar, S [1 ]
Yogeeta, SK [1 ]
Subashini, R [1 ]
Devaki, T [1 ]
机构
[1] Univ Madras, Dept Biochem, Madras 600025, Tamil Nadu, India
关键词
cyclophosphamide; squalene; enzymic antioxidants; non-enzymic antioxidants; TBARS; free radicals;
D O I
10.1016/j.cbi.2006.02.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cyclophosphamide (CP) is a widely used antineoplastic drug, which could cause toxicity of the normal cells due to its toxic metabolites. In this study, the protective role of squalene (SQ) towards the tissue defense system in the toxicity induced by CP (150 mg/kg b.w., twice, in 2 consecutive days) was studied in the experimental rats. The significant (P < 0.05) alterations in the levels of enzymic [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)] and non-enzymic antioxidants [total reduced. glutathione (GSH), Vitamin E (Vit.E), Vitamin C (Vit.C) and ceruloplasmin] of the heart, red blood cell (RBC) hemolysate and plasma were investigated in the CP toxicity. Alterations in the levels of thiobarbutric acid reactive substance (TBARS) in heart, RBC hemolysate and plasma were also observed as a measure of lipid peroxidation (LPO). These pathological alterations due to CP administration were attenuated by the oral treatment of SQ at a dose of 0.4 ml/day/rat. These observations demonstrate the protective role of SQ towards the tissue defense system of the rats in the CP induced toxicity. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:252 / 260
页数:9
相关论文
共 83 条
[1]  
Arumugam N., 1997, Indian Journal of Experimental Biology, V35, P1373
[2]   THE PECKING ORDER OF FREE-RADICALS AND ANTIOXIDANTS - LIPID-PEROXIDATION, ALPHA-TOCOPHEROL, AND ASCORBATE [J].
BUETTNER, GR .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1993, 300 (02) :535-543
[3]  
BUKOWSKI R, 1999, EUR J CANCER, V32, pS2
[4]   PROTEIN MODIFICATION BY OXIDANTS AND THE ROLE OF PROTEOLYTIC-ENZYMES [J].
DAVIES, KJA .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1993, 21 (02) :346-353
[5]  
DESAI ID, 1984, METHOD ENZYMOL, V105, P138, DOI 10.1016/S0076-6879(84)05019-9
[6]  
Dollery C., 1999, THERAPEUTIC DRUGS, P349
[7]  
Ebenezar K. K., 2001, Biomedicine, V21, P71
[8]   THE DISTRIBUTION OF ASCORBIC-ACID BETWEEN VARIOUS CELLULAR-COMPONENTS OF BLOOD, IN NORMAL INDIVIDUALS, AND ITS RELATION TO THE PLASMA-CONCENTRATION [J].
EVANS, RM ;
CURRIE, L ;
CAMPBELL, A .
BRITISH JOURNAL OF NUTRITION, 1982, 47 (03) :473-482
[9]   Squalene inhibits sodium arsenite-induced sister chromatid exchanges and micronuclei in Chinese hamster ovary-K1 cells [J].
Fan, SR ;
Ho, IC ;
Yeoh, FLF ;
Lin, CJ ;
Lee, TC .
MUTATION RESEARCH-GENETIC TOXICOLOGY, 1996, 368 (3-4) :165-169
[10]   Inhibition of neutrophil apoptosis by acrolein: a mechanism of tobacco-related lung disease? [J].
Finkelstein, EI ;
Nardini, M ;
Van der Vliet, A .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2001, 281 (03) :L732-L739