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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

1995; Elsevier BV; Volume: 76; Issue: 1 Linguagem: Inglês

10.1016/0378-4274(94)03190-8

1879-3169

Tsuyoshi Yokoi, Sekio Nagayama, Rieko Kajiwara, Yasuro KAWAGUCHI, Tatsuo Aizawa, Yumiko Otaki, Masaki Aburada, Tetsuya Kamataki,

Drug Transport and Resistance Mechanisms

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 for 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.