Hepatic P-glycoprotein changes with total parenteral nutrition administration

• Published in: JPEN. Journal of parenteral and enteral nutrition Vol. 28; no. 1; pp. 1 - 6
• Main Authors: Tazuke, Y, Kiristioglu, I, Heidelberger, KP, Eisenbraun, MD, Teitelbaum, DH
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2004; ASPEN; American Society for Parenteral and Enteral Nutrition
• Subjects: Alanine Transaminase - blood; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Aspartate Aminotransferases - blood; ATP Binding Cassette Transporter, Sub-Family B - genetics; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - analysis; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Bile Acids and Salts - blood; Biological and medical sciences; Biopsy; Cholestasis - metabolism; Emergency and intensive care: metabolism and nutrition disorders. Enteral and parenteral nutrition; Gene Expression; Genes, MDR - genetics; Intensive care medicine; Liver - chemistry; Liver - enzymology; Liver - pathology; Liver Diseases - etiology; Liver Diseases - metabolism; Male; Medical sciences; Mice; Mice, Inbred C57BL; Parenteral Nutrition, Total - adverse effects; RNA, Messenger - analysis; Nutrition; Digestive system; Rodentia; Glycoprotein; Hepatic disease; Histology; Biliary tract disease; Gene expression; Enteral administration; Parenteral administration; Feeding; Vertebrata; Mammalia; Treatment; Hepatocyte; Mouse; Animal; Cholostasis; Lacrimal canaliculus; Digestive diseases; Transport; Bile
• ISSN: 0148-6071; 1941-2444
• DOI: 10.1177/014860710402800101

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.