Rifampicin, not vitamin E, suppresses parenteral nutrition-associated liver disease development through the pregnane X receptor pathway in piglets

Autor: Gregory Guthrie, Charlotte Lauridsen, Douglas G. Burrin, Shaji Chacko, Barbara Stoll, Jogchum Plat
Přispěvatelé: Nutrition and Movement Sciences, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Parenteral Nutrition
Physiology
medicine.medical_treatment
Sus scrofa
parenteral nutrition-associated liver disease
INFANTS
vitamin E
Pharmacology
Liver Diseases/etiology
rifampicin
Liver disease
chemistry.chemical_compound
ABC TRANSPORTERS
Liver/drug effects
Cytochrome P-450 CYP3A
Glucuronosyltransferase
Phospholipids
FISH-OIL
Hyperbilirubinemia
Pregnane X receptor
Liver Diseases
ALPHA-TOCOPHEROL
Gastroenterology
Pregnane X Receptor
Cytochrome P-450 CYP3A/metabolism
Fish oil
Liver
FAT OVERLOAD SYNDROME
ACID
alfa-tocopherol
Emulsions
Rifampin
medicine.drug
Research Article
Signal Transduction
EXPRESSION
Fat Emulsions
Intravenous
Bile Acids and Salts/biosynthesis
Hyperbilirubinemia/etiology
METABOLISM
Bile Acids and Salts
03 medical and health sciences
Pregnane X Receptor/agonists
Cholestasis
Physiology (medical)
medicine
Animals
Vitamin E/pharmacology
030109 nutrition & dietetics
Hepatology
business.industry
Vitamin E
bile acid metabolism
Cholestasis/etiology
LIPID EMULSION
medicine.disease
Soybean Oil
Disease Models
Animal
030104 developmental biology
Parenteral nutrition
chemistry
Animals
Newborn
Glucuronosyltransferase/metabolism
BILE
alpha-Tocopherol
business
Rifampin/pharmacology
cholestasis
Rifampicin
Zdroj: American Journal of Physiology-Gastrointestinal and Liver Physiology, 318(1), G41-G52. American Physiological Society
Guthrie, G, Stoll, B, Chacko, S, Lauridsen, C, Plat, J & Burrin, D G 2020, ' Rifampicin, not vitamin E, suppresses parenteral nutrition-associated liver disease development through the pregnane X receptor pathway in piglets ', American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 318, no. 1, pp. G41-G52 . https://doi.org/10.1152/ajpgi.00193.2019
Am J Physiol Gastrointest Liver Physiol
ISSN: 0193-1857
0148-6071
DOI: 10.1152/ajpgi.00193.2019
Popis: Infants receiving long-term parenteral nutrition (PN) develop PN-associated liver disease (PNALD). We previously (Ng K et al. JPEN J Parenter Enteral Nutr 40: 656–671, 2016. doi: 10.1177/0148607114567900 .) showed that PN containing soy-based lipid supplemented with vitamin E (α-tocopherol) prevents the development of PNALD. We hypothesize that this occurs via vitamin E activation of pregnane X receptor (PXR)-mediated pathways involved in bile acid metabolism. Neonatal piglets received PN for 14 days containing Intralipid (IL; soy-based lipid emulsion), IL supplemented with 12.6 mg·kg−1·day−1vitamin E (VITE), or IL with 10 mg·kg−1·day−1Rifadin IV (RIF), a PXR agonist. Pigs treated with IL and VITE, but not RIF, developed cholestasis and hyperbilirubinemia, markers of liver disease. The hepatic PXR target genes CYP3A29 and UGT1A6 increased during RIF treatment. RIF also modestly increased metabolism of chenodeoxycholic acid to the more hydrophilic bile acid hyocholic acid. Serum fibroblast growth factor (FGF)-19, a key regulator in suppressing hepatic bile acid synthesis, significantly increased in the RIF group. We conclude rifampicin modified markers of PNALD development by increased metabolism of bile acids and potentially suppressed bile acid synthesis. Vitamin E was ineffective at high lipid doses in preventing PNALD.NEW & NOTEWORTHY Intravenous vitamin E and rifampicin were administered to neonatal piglets receiving parenteral nutrition to determine their efficacy in reducing the progression of parenteral nutrition-associated liver disease (PNALD). Rifampicin increased serum FGF-19 concentrations and synthesis of the bile acid hyocholic acid which led to a reduction of PNALD parameters at 2 wk of administration. This result has potential clinical implications for the use of rifampicin as a safe and inexpensive treatment for short-term development of PNALD.
Databáze: OpenAIRE
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