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 (LEG) 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.