Effect of cyclosporin A on hepatocyte proliferation after partial hepatectomy in rats: comparison with standard immunosuppressive agents.
The effects of cyclosporin A on the regenerating liver were studied in rats after partial hepatectomy and were compared with those of conventional immunosuppressants such as methylprednisolone and azathioprine. In Group I, a standard hepatectomy removing two thirds of the organ was performed. In Group II, an oral dose of 10 mg/kg of cyclosporin A was given 1 day before and immediately, 24 hours, and 48 hours after the same hepatectomy. In Groups III and IV, azathioprine and methylprednisolone were administered in 8 mg/kg doses by way of the tail vein by the same protocol as in Group II. The mortality rate, liver weight restoration, and histologic and mitotic characteristics of the liver remnants, as well as serum levels of animotransferase, total bilirubin, and creatinine were examined from 24 hours to 10 days after the operation. Azathioprine and methylprednisolone substantially suppressed hepatocyte mitosis when compared with the control group; however, cyclosporin A treatment did not inhibit, but may, in fact, have stimulated liver cell proliferation. Changes in other parameters coincided with this phenomenon. The noninhibitory effect of cyclosporin A on liver regeneration has also been discussed.
Kim
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YI
Department of Surgery, University of Cambridge, Addenbrookes Hospital, England.
Salvini
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Auxilia
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Calne
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D000818:Animals; D001379:Azathioprine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D006498:Hepatectomy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D001379:Azathioprine; D008775:Methylprednisolone