Liver regeneration is impaired by FK778 in partially hepatectomized rats, while supplemental uridine restores both liver growth and hepatocyte proliferation

Hepatology Research : the Official Journal of the Japan Society of Hepatology
Ali-Reza BiglarniaMassimo Malagó

Abstract

The impact of mandatory immunosuppression on liver regeneration after segmental liver transplantation is of clinical importance. FK778, a novel immunosuppressant, inhibits pyrimidine biosynthesis and prevents rejection after organ transplantation in a dose-dependent manner. We investigated the effect of FK778 at a highly effective dose on liver regeneration in a small animal model. Inbred Lewis rats were subjected to 70% partial hepatectomy (PH) and treated with saline (n = 28), uridine (n = 16), FK778 alone (n = 28) or in combination with uridine (n = 16). FK778 was given intravenously daily at a dose of 25 mg/kg bodyweight (bw) and uridine was given daily intraperitoneally at a dose of 250 mg/kg bw. Liver bodyweight ratio (LBR), hepatocyte proliferation index (PI), blood chemistry and morphological analysis were incorporated. PI was determined by Ki-67 immunostaining. De Ritis ratio was calculated to assess the extent of liver damage. In FK778-treated animals PI was decreased at 24 h and 72 h and LBR was lower at 48 h and 72 h (P < 0.05) after the PH. In addition, morphological analysis showed confluent central lobular necrosis at 72 h in four of seven animals. Uridine supplementation restored PI, LBR and the de Ritis ratio i...Continue Reading

References

Mar 1, 1988·Transplantation·C E BroelschJ L Lichtor
Apr 4, 1997·Science·G K Michalopoulos, M C DeFrances
Apr 1, 1997·Journal of Hepatology·N Assy, G Y Minuk
Dec 28, 1999·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·S SlausonR E Morris
Feb 10, 2000·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·J CzechH U Schorlemmer
Sep 25, 2004·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Silvio NadalinChristoph E Broelsch
Jan 1, 1997·Expert Opinion on Investigational Drugs·H T Silva, R E Morris
Mar 25, 2008·Transplantation·Tobias DeuseSonja Schrepfer

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Citations

Dec 10, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Wei-Dong ChenWendong Huang

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