Clinical usefulness of edaravone for acute liver injury.
BACKGROUND
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), lactate dehydrogenase (LDH) level (CCl4, 5068.0 +/- 2956.4 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, 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.
Tada
Shinchiro
S
Departments of Internal Medicine and Pathology, School of Medicine, Keio University and Center for Liver Diseases, Kitasato Institute Hospital, Tokyo, Japan.
Nakamoto
Nobuhiro
N
Kameyama
Kaori
K
Tsunematsu
Satoshi
S
Kumagai
Naoki
N
Saito
Hidetsugu
H
Ishii
Hiromasa
H
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008107:Liver Diseases / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D016166:Free Radical Scavengers; D002251:Carbon Tetrachloride; D000077553:Edaravone; D000983:Antipyrine