T. Yokoi et al., EFFECTS OF CYCLOSPORINE-A AND D-PENICILLAMINE ON THE DEVELOPMENT OF HEPATITIS AND THE PRODUCTION OF ANTIBODY TO PROTEIN DISULFIDE-ISOMERASEIN LEC RATS, Research communications in molecular pathology and pharmacology, 85(1), 1994, pp. 73-81
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.