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Insulin-like growth factor-I enhances choleretic action of FK506 in rats.

Abstract：

:FK506 is an immunosuppressant for organ transplantation in the same clinical settings as cyclosporine (CsA). In the management of liver transplantation, FK506 has advantages over CsA, in terms of rejection and corticosteroid requirements. Recent clinical findings in liver transplant patients indicate that FK506, but not CsA, stimulates choleresis, suggesting that FK506 treatment may accelerate recovery from cholestatic dysfunction through its choleretic action. Recently, we demonstrated in rats that exogenous treatment with insulin-like growth factor I (IGF-I) results in an increase in bile flow and also that FK506 has the potential to increase hepatic production of IGF-I. However, circulating levels of IGF-I in FK506-treated rats were only 30% higher than in nontreated rats. In this study, we evaluated the combined effect of treatment with both IGF-I and FK506 on bile flow in rats to explore the possibility that combination treatment in liver transplant patients could enhance the choleretic action of FK506, benefiting the transplanted liver. Combination treatment of IGF-I with FK506 resulted in a potent and long-lasting increase in bile flow. Overall, this study demonstrated that IGF-I treatment enhanced the choleretic action of FK506, providing potential clinical utility for combination therapy using these two drugs, in treatment after liver transplantation.

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Mabuchi M,Kawamura I,Takeshita S,Fushimi M,Takakura S,Hirosumi J,Mutoh S

doi

10.1016/s0041-1345(03)00358-0

subject

Has Abstract

pub_date

2003-06-01 00:00:00

pages

1596-8

issue

4

eissn

0041-1345

issn

1873-2623

pii

S0041134503003580

journal_volume

35

pub_type

杂志文章

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