[The protective effect of (4R)-hexahydro-7, 7-dimethyl-6-oxo-1, 2, 5-dithiazocine-4-carboxylic acid (SA3443), a novel cyclic disulfide, on acetaminophen-induced liver injury].
Effects of (4R)-hexahydro-7, 7-dimethyl-6-oxo-1, 2, 5-dithiazocine-4-carboxylic acid (SA3443) on acetaminophen-induced liver injury were investigated in BALB/c mice. SA3443 (30-300 mg/kg, p.o.) dose-dependently suppressed the elevation of serum transaminase activities and the histological changes of liver induced by acetaminophen (150 mg/kg, p.o.). The compound at the same doses also reduced the mortality due to the lethal acute hepatic failure induced by acetaminophen (350 mg/kg, p.o.). Other hepatoprotective agents, cianidanol (500 mg/kg, p.o.), malotilate (100 mg/kg, p.o.), grycyrrhizine (10 mg/kg, i.p.) and cysteine (300 mg/kg, p.o.) similarly reduced it. SA3443 had no effect on glutathione (GSH) contents in the liver of normal mice, but it dose-dependently suppressed the decrease of GSH contents in the liver of BALB/c mice treated with acetaminophen. These results suggest that SA3443, a novel cyclic disulfide, provides considerable protection against acetaminophen-induced liver injury and that one of the modes of the hepatoprotective action of this compound is suppression of the decrease of GSH contents in the liver.
Tanaka
M
M
Central Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Nakata
K
K
Takase
K
K
Mita
S
S
D000082:Acetaminophen; D000818:Animals; D001392:Azocines / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D004220:Disulfides / Q000627:therapeutic use*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013438:Sulfhydryl Compounds / Q000378:metabolism
D001392:Azocines; D004220:Disulfides; D013438:Sulfhydryl Compounds; C069788:SA 3443; D000082:Acetaminophen