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Hepatic P‐glycoprotein changes with total parenteral nutrition administration
Author(s) -
Tazuke Y,
Kiristioglu I,
Heidelberger KP,
Eisenbraun MD,
Teitelbaum DH
Publication year - 2004
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/014860710402800101
Subject(s) - cholestasis , medicine , p glycoprotein , parenteral nutrition , liver injury , endocrinology , liver disease , bile acid , biology , gene expression , messenger rna , saline , gene , multiple drug resistance , biochemistry , antibiotics
BACKGROUND: The mechanism(s) responsible for the development of parenteral nutrition‐associated liver disease (PNALD) is unknown. Recently, a number of bile canalicular transport proteins have been identified that transport bile components out of hepatocytes. One group of these genes, multidrug resistance 1 (mdr1) and mdr2, encode P‐glycoproteins. Mice lacking mdr2 expression develop liver disease that appears similar to PNALD. This study investigated the alteration in the expression of these transport proteins during the administration of total parenteral nutrition (TPN). METHODS: Mice received either physiologic saline and standard chow or TPN. Mice were sacrificed on day 7, and hepatic DNA and RNA content, mRNA expression, and levels of mdr1 and mdr2 proteins were measured. RESULTS: TPN administration led to a significant (p <.05) decline in mdr2 mRNA expression and an increase in mdr1 mRNA expression. Mdr2 protein expression declined by 66% in the TPN‐treated group, and mdr1 protein expression significantly increased by 58%. Histology and biochemical parameters showed no evidence of liver injury. Serum bile acid levels were elevated in the TPN group, suggesting the development of early cholestasis. CONCLUSIONS: The decline in mdr2 and rise in mdr1 mRNA and protein expression with TPN administration occurred before the development of liver injury but during an early state of cholestasis. This suggests that alterations in mdr gene expression may be a causative factor in the development of PNALD.