Effects of methyl (+)(3S)-1,2,3,4-tetrahydro-3-hydroxy-methyl-beta-carboline-2- carbodithioate (THC), a new hepatoprotective agent, on acute liver injuries induced by various hepatotoxic substances in mice and rats.
The effects of oral administration of methyl (+)(3S)-1,2,3,4-tetrahydro-3-hydroxymethyl-beta-carboline-2-carbodith ioate (THC) on acute liver injuries induced by carbon tetrachloride (CCl4), bromobenzene (B.B.), D-galactosamine (GALN) and alpha-naphthylisothiocyanate (ANIT) in rats and allyl alcohol (A.A.) in mice were studied. THC suppressed the elevation of plasma transaminase activities and hepatic lipid contents induced by CCl4 in rats when the animals were treated with THC for 4 consecutive days simultaneously with CCl4 administration. THC also suppressed the elevation of hepatic lipid contents induced by the 4 d-treatment of rats with CCl4 when administered for 4 consecutive days from the next day after treatment with CCl4. This effect of THC was histopathologically confirmed. In addition, pretreatment with THC protected rats against liver injuries induced by B.B., GALN, and ANIT, but not against A.A. in mice. This protection was evident from the suppression of elevated activities of plasma transaminase and/or elevated contents of hepatic lipid induced by these hepatotoxic substances. Furthermore, THC inhibited the formation of lipid peroxide in rat liver microsomes with an IC50 of 3.2 microM. These results suggested that THC protected rats against liver injuries induced by CCl4, B.B., GALN and ANIT and had a protective effect on the microsomal membrane against lipid peroxide in vitro.
Matsumoto
M
M
Safety Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Matsuoka
Y
Y
Saiga
Y
Y
Iijima
I
I
D015058:1-Naphthylisothiocyanate / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001969:Bromobenzenes / Q000633:toxicity; D002243:Carbolines / Q000494:pharmacology*; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D005688:Galactosamine / Q000633:toxicity; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014280:Triglycerides / Q000097:blood
D001969:Bromobenzenes; D002243:Carbolines; D008054:Lipid Peroxides; D014280:Triglycerides; D015058:1-Naphthylisothiocyanate; D005688:Galactosamine; C055561:methyl 1,2,3,4-tetrahydro-3-hydroxymethyl-beta-carboline-2-carbodithioate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase