Inhibitory effect of TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11- methylenedioxy-6-dibenzo[a,c]cyclooctenol) on immunologically induced liver injuries.
TJN-101, which is a lignan component isolated from schisandra fruits, inhibits hepatotoxic chemicals-induced liver injuries. In this study, effects of TJN-101 on immunologically induced liver injuries were investigated in vivo and in vitro. When a small dose of lipopolysaccharide was injected into mice previously injected with heat-killed Propionibacterium acnes, most of the animals died with acute hepatic failure which was produced by cytotoxic factors from activated adherent cells, and liver cells were injured by antibody-dependent cell-mediated cytotoxic (ADCC) reaction or activated macrophages in vitro. TJN-101 reduced the mortality of the mice with acute hepatic failure dose-dependently. Histologically, necrosis was suppressed by the treatment of TJN-101, but infiltration of non-specific inflammatory cells was not. TJN-101 inhibited the isolated liver cell injuries induced by ADCC reaction or activated macrophages in vitro. These results suggest that TJN-101 can be markedly protective against immunological liver injuries.
Ohkura
Y
Y
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
Mizoguchi
Y
Y
Sakagami
Y
Y
Kobayashi
K
K
Yamamoto
S
S
Morisawa
S
S
Takeda
S
S
Aburada
M
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D034242:Cyclooctanes; D004149:Dioxoles; D006168:Guinea Pigs; D017705:Lignans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008107:Liver Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism
D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; D008070:Lipopolysaccharides; D011083:Polycyclic Compounds; D011506:Proteins; C033585:schizandrol B; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase