Rifampicin, Not Vitamin E, Suppresses Parenteral Nutrition Associated Liver Disease Development through Pregnane X Receptor Pathway in Piglets.

Rifampicin, Not Vitamin E, Suppresses Parenteral Nutrition Associated Liver Disease Development through Pregnane X Receptor Pathway in Piglets. Am J Physiol Gastrointest Liver Physiol. 2019 Oct 11;: Authors: Guthrie G, Stoll B, Chacko S, Lauridsen C, Plat J, Burrin DG Abstract Infants receiving long-term parenteral nutrition (PN) develop PN associated liver disease (PNALD). We previously 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 d containing Intralipid (IL, soy-based lipid emulsion), IL supplemented with 12.6 mg/kg*d-1 vitamin E (VITE), or IL with 10 mg/kg*d-1 Rifadin 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. Vitam...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research