Influence of immunosupressive drugs on liver regeneration after partial hepatectomy in rats - experimental studies
Wojciech G. Polak
Med Sci Monit 1999; 5(3): BR405-409
The aim of this study was to asses the influence of selected immunosuppressants on liver regeneration in rats. Material and methods: In sixty male Buffalo strain rats partial hepatectomy (60-65%) was carried out according to Higgins and Anderson under ether anaesthesia. The observation of the rats lasted 6 weeks and 42 days after operation all animals were sacrificed. Rats were randomly assigned to one of six group (10 rats per group) and treated as follows: group 1 - without immunosuppressant (control group), group 2 - cyclosporin A, group 3 - azathioprine, group 4 - tacrolimus, group 5 - prednisolone, group 6 - triple drug therapy (TDT) - azathioprine with cyclosporin A and prednisolone. All rats in each group had following laboratory investigations in blood serum: aspartate aminotransferase (AspAT) activity, alanine aminotransferase (AlAT) activity and alkaline phosphatase (AP) activity. The above parameters were assessed one day before operation and then in 21st and 42nd day after hepatectomy. After 42 days observation all rats were killed and the remnant liver were removed for investigation of hepatic restoration and histologic features. Histologic examination of all sections was performed in light microscope. Furthermore resected liver tissue was weighed the day of operation and also the remnant liver was weighed after sacrification of the animal to calculate the regenerative rate. When applicable the comparison for statistical significance was performed according to the Student's test, Scheffe's test and analysis of variance. A p value of<0.05 was considered to represent a significant difference. Result and conclusions. Regenerative rate of liver tissue was significantly higher in rats treated with cyclosporin A and tacrolimus and significantly lower in rats treated with prednisolone and TDT. There were no significant difference between control group and rats treated with azathioprine. All immunosupressants used in this study influenced on liver function parameters as AspAT, AlAT and AP activity, but the changes were temporary. Histologic examination revealed in 3 rats treated with cyclosporin A restoration nodules with hepatocytes regeneration. In two rats treated with azathioprine there was observed adenocarcinoma coming from bile ducts. One rat treated with tacrolimus presented acute, diffuse necrosis of central parts of hepatic lobules. This study has shown that among immunosupressant used in this experiment only cyclosporin A and tacrolimus stimulated liver regeneration after partial hepatectomy. On the other hand prednisolone and triple drug therapy inhibited liver regeneration, whereas azathioprine had no influence on liver restoration. In some rats treated with cyclosporin A restoration nodules with hepatocytes regeneration occured. In rats receiving azathioprine there were observed two cases of cholangiocarcinoma.
Keywords: Rat, histological examination, regenerative rate, regenerative rate, Tacrolimus, Steroids, Steroids, azathioprine