The hepatotropic influence of cyclosporine.
The effect of cyclosporine on liver regeneration has been investigated in 25 dogs that underwent an end-to-side portacaval shunt (Eck fistula) followed by 4 days continuous infusion of the drug into the left branch of the portal vein. Three different cyclosporine infusion rates were used: 0.06, 0.6, and 4.0 mg/kg/day. Control animals received the intravenous vehicle of cyclosporine at the same rate as the treated animals; a second control group received insulin, 0.42 units/kg/day. Hepatocyte 3H-thymidine-labeled mitoses (index of hyperplasia) and hepatocyte volume (index of hypertrophy) were studied in the left (infused) and right (control) lobes in each animal. Cyclosporine vehicle had no measurable effect on hepatocytes that suffered typical atrophy and moderate increase in mitotic index after the Eck fistula. Cyclosporine infusion stimulated cell renewal significantly and restored hepatocyte size in the infused lobes with a dose-response relation. Similar positive effects were observed in the right (nonperfused) lobes, although they were less than those in the left (infused) lobes. This was because of an unmistakable spillover of cyclosporine from the infused lobes, especially in the large-dose group. No sign of hepatotoxicity was detected at any cyclosporine infusion rate. Cyclosporine has a remarkable hepatotropic effect that may be helpful in the context of liver transplantation.
Department of Surgery, School of Pharmacy, University Health Center of Pittsburgh, Pa.
V
V
Mazzaferro
K A
KA
Porter
C L
CL
Scotti-Foglieni
R
R
Venkataramanan
L
L
Makowka
L
L
Rossaro
A
A
Francavilla
S
S
Todo
D H
DH
Van Thiel
T E
TE
Starzl
D000818:Animals; D003524:Cyclosporins / Q000097:blood / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D007328:Insulin / Q000494:pharmacology; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000187:drug effects; D014677:Pharmaceutical Vehicles / Q000494:pharmacology
D003524:Cyclosporins; D007328:Insulin; D014677:Pharmaceutical Vehicles