Hepatoprotective effects of 1-[(2-thiazolin-2-yl)-amino]acetyl-4-(1,3-dithiol-2-ylidene)-2,3,4,5- tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) in various experimental liver injuries.
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.
Yoshitake
I
I
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Ohishi
E
E
Kubo
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001552:Benzazepines / Q000627:therapeutic use*; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D005001:Ethionine; D005688:Galactosamine; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011425:Propionibacterium acnes; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000627:therapeutic use*; D014280:Triglycerides / Q000378:metabolism
D001552:Benzazepines; D008070:Lipopolysaccharides; D013844:Thiazoles; D014280:Triglycerides; C074412:KF 14363; D005688:Galactosamine; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005001:Ethionine