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Hepatoprotective effects of KF-14363 were investigated in the following experimental models. KF-14363 inhibited the increase in serum glutamate pyruvate transaminase (GPT) dose-dependently, and a significant inhibition was noted at a dose of 30 mg/kg or more. KF-14363 significantly inhibited the D-galactosamine (D-gal)-induced increase in serum transaminase by oral administration at 250 mg/kg x 1 and 250 mg/kg x 2 doses. The D-gal-induced decrease in total protein levels was inhibited at doses of 100 mg/kg x 2 and 250 mg/kg x 2. KF-14363 (100 mg/kg or more) significantly inhibited the increase in liver triglyceride levels induced by DL-ethionine (250 mg/kg x 3). KF-14363 (300 mg/kg) significantly inhibited the D-gal plus lipopolysaccharide-induced increase in GPT. At 100 mg/kg or less, however, an inhibiting tendency was noted, which was not significant as the values varied widely. KF-14363 (100 mg/kg) significantly inhibited Propionibacterium acnes plus lipopolysaccharide-induced mortality at 7 and 8 hr, and it showed an inhibitory tendency at 24 hr. These results demonstrate that KF-14363 is a compound that has a protective effect against the damage induced in various experimental liver injury models with different mechanisms.

japanese journal of pharmacology/japanese journal of pharmacology

Hepatoprotective Effects of l-[(2-Thiazolin-2-yl)-amino]acetyl-4-(l,3-dithiol-2-ylidene)-2,3,4,5-tetrahydrolH-l-benzazepin-3,5-dione Hydrochloride (KF-14363) in Various Experimental Liver Injuries