Clinical usefulness of edaravone for acute liver injury

被引:33
作者
Tada, S
Nakamoto, N
Kameyama, K
Tsunematsu, S
Kumagai, N
Saito, H
Ishii, H
机构
[1] Keio Univ, Sch Med, Dept Internal Med, Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Pathol, Tokyo 160, Japan
[3] Kitasato Inst Hosp, Ctr Liver Dis, Tokyo, Japan
关键词
acute liver injury; apoptosis; carbon tetrachloride; free radicals; steatosis;
D O I
10.1046/j.1440-1746.2003.03064.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and Aims: Edaravone, a newly synthesized radical scavenger, has shown an excellent effect on treating stroke patients. The effect of edaravone on carbon tetrachloride (CCl4)-induced acute liver injury was examined. Methods: Six rats were injected with CCl4 alone and six rats were intravenously injected with edaravone immediately after and 3 h after injection of CCl4 . Another six rats were injected with olive oil alone. The animals were killed at 24 h after the CCl4 injection. Results: Injection of CCl4 was followed by a marked increase in serum alanine aminotranferase (ALT) level (CCl4, 1630.6+/-606.8 IU/L; olive oil, 21.0+/-2.6 IU/L; P<0.001),<LF>lactate dehydrogenase (LDH) level (CCl4, 5068.0+/-2956.4 <LF>IU/L; olive oil, 203.6+/-30.5 IU/L; P<0.005), and total bilirubin (TB) level (CCl4, 0.88+/-0.48 mg/dL; olive oil, <LF>0.37+/-0.05 mg/dL; P<0.01), whereas in the edaravone-treated rats, the ALT (119.4+/-113.5 IU/L, P<0.001), LDH (369.7+/-288.2 IU/L, P<0.005), and TB values (0.29+/-0.16 mg/dL, P<0.01) were significantly decreased. Histological examination of the liver by hematoxylin and eosin and oil red O staining showed a marked reduction of steatosis in the CCl4 and edaravone-treated rats compared with the CCl4 -injected rats. Significant inhibition of hepatocytic apoptosis was demonstrated by the terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling (TUNEL) method in the edaravone-treated rats. Conclusions:These results suggest that edaravone has a marked preventive effect on oxidative stress-induced acute liver injury. (C) 2003 Blackwell Publishing Asia Pty Ltd.
引用
收藏
页码:851 / 857
页数:7
相关论文
共 45 条
[1]   STRONG ATTENUATION OF ISCHEMIC AND POSTISCHEMIC BRAIN EDEMA IN RATS BY A NOVEL FREE-RADICAL SCAVENGER [J].
ABE, K ;
YUKI, S ;
KOGURE, K .
STROKE, 1988, 19 (04) :480-485
[2]   Free radical mechanisms in immune reactions associated with alcoholic liver disease [J].
Albano, E .
FREE RADICAL BIOLOGY AND MEDICINE, 2002, 32 (02) :110-114
[3]  
ANDUS T, 1991, HEPATOLOGY, V13, P364, DOI 10.1016/0270-9139(91)92454-G
[4]   Aloe-emodin quinone pretreatment reduces acute liver injury induced by carbon tetrachloride [J].
Arosio, B ;
Gagliano, N ;
Fusaro, LMP ;
Parmeggiani, L ;
Tagliabue, J ;
Galetti, P ;
De Castri, D ;
Mocheni, C ;
Annoni, G .
PHARMACOLOGY & TOXICOLOGY, 2000, 87 (05) :229-233
[5]   Role of glutathione, lipid peroxidation and antioxidants on acute bile-duct obstruction in the rat [J].
Barón, V ;
Muriel, P .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1999, 1472 (1-2) :173-180
[6]   CCL4-INDUCED TOXICITY IN ISOLATED HEPATOCYTES - THE IMPORTANCE OF DIRECT SOLVENT INJURY [J].
BERGER, ML ;
BHATT, H ;
COMBES, B ;
ESTABROOK, RW .
HEPATOLOGY, 1986, 6 (01) :36-45
[7]  
BRATTIN W J, 1985, Journal of Free Radicals in Biology and Medicine, V1, P27, DOI 10.1016/0748-5514(85)90026-1
[8]   Reduction of carbon tetrachloride-induced rat liver injury by IRFI 042, a novel dual vitamin E-like antioxidant [J].
Campo, GM ;
Squadrito, F ;
Ceccarelli, S ;
Calò, M ;
Avenoso, A ;
Campo, S ;
Squadrito, G ;
Altavilla, D .
FREE RADICAL RESEARCH, 2001, 34 (04) :379-+
[9]   AN INTRODUCTION TO FREE-RADICAL BIOCHEMISTRY [J].
CHEESEMAN, KH ;
SLATER, TF .
BRITISH MEDICAL BULLETIN, 1993, 49 (03) :481-493
[10]  
CHVAPIL M, 1972, P SOC EXP BIOL MED, V141, P150