AI Article Synopsis

  • The study aimed to investigate how cyclosporin A (CyA), an immunosuppressive drug, affects metabolism and liver regeneration in rats after a significant surgical removal of the liver (70% hepatectomy).
  • Rats were divided into three groups receiving different doses of CyA, and their liver regeneration and CyA serum levels were analyzed over a period after surgery.
  • Results showed that higher doses of CyA enhanced liver regeneration but also indicated a decrease in the metabolic activity of CyA over time, which could complicate dosing during liver transplantation recovery.

Article Abstract

Aim: To elucidate the metabolism and the effect of the cyclosporin A (CyA) as a representative immunosuppressive drug used in transplantation in a partially hepatectomized rat model.

Methods: CyA was administered to rats that underwent a 70% hepatectomy. These rats were randomly assigned into three groups according to the dose of CyA administration as follows; (group 1) water, (group 2) 5 mg/kg CyA, (group 3) 10 mg/kg CyA. On postoperative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver regeneration ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-polymerase chain reaction method to determine albumin and cytochrome p450 expression.

Results: The serum concentration of CyA in group 3 was significantly higher than group 2 during liver regeneration. CyA enhanced the liver regeneration in a dose dependent manner. The mRNA expression associated with CyA metabolism was significantly decreased on day 14, while preserving the albumin producing activity.

Conclusion: These data indicate that the p-450 activity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepatectomy, which may, therefore, be linked to difficulty in controlling the optimal dose of CyA during early period of LDLT.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766117PMC
http://dx.doi.org/10.3748/wjg.14.6355DOI Listing

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