Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Nov 7, 2008; 14(41): 6355-6359
Published online Nov 7, 2008. doi: 10.3748/wjg.14.6355
Metabolism for cyclosporin A during liver regeneration after partial hepatectomy in rats
Shigeki Nagayoshi, Yujo Kawashita, Susumu Eguchi, Yukio Kamohara, Mitsuhisa Takatsuki, Shungo Miyamoto, Satoshi Mochizuki, Akihiko Soyama, Hirotaka Tokai, Masaaki Hidaka, Yoshitsugu Tajima, Takashi Kanematsu
Shigeki Nagayoshi, Yujo Kawashita, Susumu Eguchi, Yukio Kamohara, Mitsuhisa Takatsuki, Shungo Miyamoto, Satoshi Mochizuki, Akihiko Soyama, Hirotaka Tokai, Masaaki Hidaka, Yoshitsugu Tajima, Takashi Kanematsu, Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan
Author contributions: Nagayoshi S, Kawashita Y, Eguchi S, Kamohara Y, Takatsuki M, Miyamoto S, Mochizuki S, Soyama A, Tokai H, Hidaka M, Tajima Y, and Kanematsu T designed research; Nagayoshi S performed research; Nagayoshi S and Kawashita Y analyzed data; and Nagayoshi S, Kawashita Y, and Kanematsu T wrote the paper.
Correspondence to: Susumu Eguchi, MD, Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. sueguchi@net.nagasaki-u.ac.jp
Telephone: +81-95-8197316 Fax: +81-95-8197319
Received: May 21, 2008
Revised: September 16, 2008
Accepted: September 23, 2008
Published online: November 7, 2008
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.

Keywords: Cyclosporin A; Liver regeneration; Partial hepatectomy; Rat