Effects of cyclosporin-A and D-penicillamine on the development of hepatitis and the production of antibody to protein disulfide isomerase in LEC rats.
Long Evans Cinnamon (LEC) rats, which spontaneously develop hepatitis, produce an autoantibody to protein disulfide isomerase (PDI) before the development of clinical signs of hepatitis. Anti-PDI antibody may be associated with immunological hepatitis. Thus, the purpose of this study was to investigate the effects of some drugs on the development of hepatitis and the occurrence of the antibody in LEC rats. Cyclosporin-A, an immunosuppressant, and D-penicillamine, which promotes copper excretion, were orally administered to LEC rats for 23 weeks. Mortality, blood biochemical parameters and the titer of serum anti-PDI antibody 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 group died at the age of 20 weeks. When rats were treated with D-penicillamine, the development of clinical signs of hepatitis was inhibited, and all rats survived. Cyclosporin-A-treated rats showed increases in blood biochemical parameters similar to those in control rats. The titer of anti-PDI antibody in control rats was higher the non-survivors than survivors. These findings suggest the association of the anti-PDI antibody with lethality, but not with the apparent development and progression of hepatitis as measured by blood biochemical parameters in LEC rats.
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
T
T
Yokoi
S
S
Nagayama
R
R
Kajiwara
Y
Y
Kawaguchi
T
T
Kamataki
D000284:Administration, Oral; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001774:Blood Chemical Analysis; D001835:Body Weight; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006520:Hepatitis, Animal / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D007535:Isomerases / Q000276:immunology*; D010396:Penicillamine / Q000008:administration & dosage / Q000494:pharmacology*; D019704:Protein Disulfide-Isomerases; D011863:Radioimmunoassay; D051381:Rats; D011922:Rats, Mutant Strains; D015996:Survival Rate
D001323:Autoantibodies; D016572:Cyclosporine; D007535:Isomerases; D019704:Protein Disulfide-Isomerases; D010396:Penicillamine