Occurrence of autoimmune antibodies to liver microsomal proteins associated with lethal hepatitis in LEC rats: effects 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 the development of hepatitis and the autoantibodies.
Long Evans Cinnamon (LEC) rats, that spontaneously develop hepatitis, were found to possess autoantibodies to liver microsomal proteins (anti-LM) before the development of hepatitis. Anti-LM antibody was assumed to appear in association with the lethal hepatitis in the LEC rats. Thus, the purpose of this study was to investigate the effects of an anti-hepatitis drug on the development of hepatitis and the occurrence of the antibody in LEC rats. Mortality, blood biochemical parameters and the titer of serum anti-LM antibody were measured. In control LEC rats, 4 of 8 rats died before 20 weeks of age. In rats treated with 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), 4 of 7 rats died of hepatitis, but the time of death was delayed by 7-10 weeks compared to the control rats. The titer of the anti-LM antibody increased 3-7 weeks before death in the non-survivors in control and TJN-101-treated rats, supporting the idea that anti-LM antibody occurs in association with acute lethal hepatitis.
Yokoi
T
T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Nagayama
S
S
Kajiwara
R
R
Kawaguchi
Y
Y
Aizawa
T
T
Otaki
Y
Y
Aburada
M
M
Kamataki
T
T
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000187:drug effects; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology* / Q000401:mortality; D001835:Body Weight / Q000187:drug effects; D034242:Cyclooctanes; D004149:Dioxoles / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006520:Hepatitis, Animal / Q000097:blood / Q000276:immunology* / Q000401:mortality; D017705:Lignans; D008862:Microsomes, Liver / Q000276:immunology*; D051381:Rats
D001323:Autoantibodies; D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; C033585:schizandrol B