EFFECTS OF 2,2'-AZOBIS (2-AMIDINOPROPANE) HYDROCHLORIDE INVIVO AND PROTECTION BY VITAMIN-E

被引:46
作者
DOOLEY, MM [1 ]
SANO, N [1 ]
KAWASHIMA, H [1 ]
NAKAMURA, T [1 ]
机构
[1] EISAI & CO LTD,EISAI RES LABS,KOISHIKAWA 4,BUNKYO KU,TOKYO 112,JAPAN
关键词
2; 2′-Azobis (2-amidinopropane) hydrochloride; Free radicals; HPLC; Lipid peroxidation; rats; TBA-reactive substances; Trolox; Vitamin E;
D O I
10.1016/0891-5849(90)90028-H
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
2,2′-Azobis (2-amidinopropane) hydrochloride (AAPH), a compound that decomposes spontaneously to generate free radicals, was administered intraperitoneally to rats. High doses (≧70 mg/kg) were always fatal within a few hours. At nonlethal levels, AAPH was found to be absorbed into the circulation where it remained with a half-life of about 30 min. Lipid peroxidation was observed to occur in the liver and, to a much smaller extent, the kidney and heart of treated rats; levels of thiobarbituric acid-ractive substances were unchanged in the lung and brain, and significantly reduced in the plasma. Serum lipid levels were also lower in the AAPH-treated rats. Orally administered vitamin E, but not its water soluble analog, prevented the accumulation of TBA-reactive substances in the livers of AAPH-treated rats in a dose-dependent manner, but had no effect on mortality or the changes in serum lipid levels. The data suggest that intraperitoneally administered AAPH is absorbed into the circulation and can induce lipid peroxidation in vivo, but that toxicity may also arise through nonradical mechanisms. Furthermore, the free radical toxicity of AAPH in vivo may not so be general as previously suggested. © 1990.
引用
收藏
页码:199 / 204
页数:6
相关论文
共 12 条
[1]  
Barclay, Ingold, Antioxidation of biological molecules. 2. The autoxidation of a model membrane. A comparison of the autoxidation of egg lecithin phosphatidylcholine in water and chlorobenzene, J. Am. Chem. Soc., 103, pp. 6478-6485, (1981)
[2]  
Yamamoto, Niki, Eguchi, Kamiya, Shimasaki, Oxidation of biological membranes and its inhbition: free radical oxidation of erythrocyte ghost membranes by oxygen, Biochim. Biophys. Acta, 819, pp. 29-36, (1985)
[3]  
Tami, Miki, Yasuda, Maeda, Mino, Effects of α-tocopherol on membrane oxdation in red blood cells, Clinical and nutritional aspects of vitamin E., pp. 317-320, (1987)
[4]  
Wayner, Burton, Ingold, Barclay, Locke, The relative contributions of vitamin E urate ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma, Biochimica et Biophysica Acta (BBA) - General Subjects, 924, pp. 408-409, (1987)
[5]  
Terao, Niki, Damage to biological tissues induced by radical initiator 2,2′-azobis-(2-amidinopropane) dihydrochloride and its inhibition by chain-breaking antioxidants, J. Free Radicals Biol. Med., 2, pp. 193-201, (1986)
[6]  
Niki, Takahashi, Tsuchiya, Komuro, Ito, Terao, Oxidation of lipids. XV. Role of hydrophilic diarylamines as antioxidants in the oxidations of lipids and biological tissues, Chem.-Biol. Interactions, 67, pp. 81-93, (1988)
[7]  
Uchiyama, Mihara, Determination of malondialdehyde precursor in tissues by thiobarbituric acid test, Anal. Biochem., 86, pp. 271-278, (1979)
[8]  
Wong, Knight, Hopfer, Zahaira, Leach, Sunderman, Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct, Clin. Chem., 33, pp. 214-220, (1987)
[9]  
Kosugi, Kikugawa, Potential thiobarbituric acid-reactive substances in peroxidized lipids, Free Radical Biol. Med., 7, pp. 205-207, (1989)
[10]  
Yagi, Lipid peroxides and human diseases, Chem. Phys. Lipids, 45, pp. 337-351, (1987)