EFFECTS OF CYCLOSPORINE-A AND D-PENICILLAMINE ON THE DEVELOPMENT OF HEPATITIS AND THE PRODUCTION OF ANTIBODY TO PROTEIN DISULFIDE-ISOMERASEIN LEC RATS

Long Evans Cinnamon (LEC) rats, which spontaneously develop hepatitis, produce an autoantibody to protein disulfide isomerase (PDI) before t he development of clinical signs of hepatitis. Anti-PDI antibody may b e associated with immunological hepatitis. Thus, the purpose of this s tudy was to investigate the effects of some drugs on the development o f hepatitis and the occurrence of the antibody in LEC rats. Cyclospori n-A, an immunosuppressant, and D-penicillamine, which promotes copper excretion, were orally administered to LEC rats for 23 weeks. Mortalit y, blood biochemical parameters and the titer of serum anti-PDI antibo dy were measured. In control LEC rats, four of eight rats died before 20-weeks-old. Only one of seven rats in the cyclosporin-A-treated grou p died at the age of 20 weeks. When rats were treated with D-penicilla mine, the development of clinical signs of hepatitis was inhibited, an d all rats survived. Cyclosporin-A-treated rats showed increases in bl ood biochemical parameters similar to those in control rats. The titer of anti-PDI antibody in control rats was higher the non-survivors tha n survivors. These findings suggest the association of the anti-PDI an tibody with lethality, but not with the apparent development and progr ession of hepatitis as measured by blood biochemical parameters in LEC rats.