Metabolism for cyclosporin A during liver regeneration after partial hepatectomy in rats

AIM: To elucidate the metabolism and the effect of the cyclosporin A (CyA) as a representative immuno-suppressive drug used in transplantation in a partially hepatectomized rat model. METHODS: CyA was administered to rats that under- went 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 post- operative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver re- generation ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-poly- merase 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 associ- ated with CyA metabolism was signifi cantly decreased on day 14, while preserving the albumin producing activity. CONCLUSION: These data indicate that the p-450 ac-tivity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepa- tectomy, which may, therefore, be linked to diffi culty in controlling the optimal dose of CyA during early period of LDLT.

AIM： To elucidate the metabolism and the effect of the cyclosporin A （CyA） as a representative immuno- suppressive 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 I） 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-poly- merase 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.