The protective effect of cyclosporine against cirrhotic alteration of the liver.
We have successfully applied the immunosuppressive drug cyclosporine in patients with primary biliary cirrhosis and in some patients with chronic active hepatitis. After several years of treatment, we have found a histologic remission tendency in cirrhotic alteration of some patients. This observation indicates that cyclosporine could have protective effects against fibrosis or cirrhotic alteration. To clarify this, we treated Sprague-Dawley rats in which the cirrhotic alteration of the liver was induced by injection of 0.5 ml/kg body weight carbon tetrachloride intramuscularly twice a week with cyclosporine (orally); the control animals were given saline solution instead of cyclosporine. After 6 weeks, we examined the liver histologically to determine the grade of fibrosis and cirrhosis and the grade of fatty degeneration; in group 2 we gave 1 mg/kg body weight cyclosporine daily, and in group 3 it was given every second day. We found excellent protective effects of cyclosporine against cirrhotic alteration in both groups compared with the control group. In group 3 only 25% of the animals showed grade 3 fibrosis and cirrhosis; however, the rate in the control animals (group 4) was 64.3%. In the daily application of cyclosporine (group 2) we found reduced effects of the drug compared with group 3. In group 1 we ordered 10 mg/kg body weight cyclosporine, which causes severe hepatotoxicity. In group 5, animals with hepatic damage from carbon tetrachloride were treated from the third week with cyclosporine. The effect of cyclosporine was not as beneficial compared with the groups in which we ordered cyclosporine from the first week. These results suggest excellent anticirrhotic effects of cyclosporine. This drug should be ordered as early as possible in the treatment of chronic hepatic damage and in an adequate minimal dosage.
Lie
T S
TS
Department of Surgery, University of Bonn, Germany.
Preissinger
H
H
Bach
M
M
Vogel
J
J
Ogawa
K
K
Kroeger
T
T
Brunner
G
G
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001835:Body Weight; D002252:Carbon Tetrachloride Poisoning / Q000150:complications / Q000473:pathology*; D003094:Collagen / Q000032:analysis; D016572:Cyclosporine / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D016572:Cyclosporine; D003094:Collagen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin