Prophylactic Intra-Uterine β-Cyclodextrin Administration during Intra-Uterine Ureaplasma parvum Infection Partly Prevents Liver Inflammation without Interfering with the Enterohepatic Circulation of the Fetal Sheep

• Published in: Nutrients Vol. 12; no. 5; p. 1312
• Main Authors: Heymans, Cathelijne, Heij, Lara R, Lenaerts, Kaatje, den Dulk, Marcel, Hadfoune, Mhamed, van Heugten, Chantal, Spiller, Owen B, Beeton, Michael L, Stock, Sarah J, Jobe, Alan H, Payne, Matthew S, Kemp, Matthew W, Kramer, Boris W, Plat, Jogchum, van Gemert, Wim G, Wolfs, Tim G A M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.05.2020; MDPI
• Subjects: Acids; Animals; Anti-inflammatory agents; beta-Cyclodextrins; Bile; Bile acids; Cesarean section; Cholesterol - administration & dosage; Cholesterol - analogs & derivatives; Cholesterol - pharmacology; Chorioamnionitis; Chorioamnionitis - drug therapy; Chorioamnionitis - microbiology; Cyclodextrins; Disease Models, Animal; Drug Carriers; Enterocolitis; Enterocolitis, Necrotizing - microbiology; Enterocolitis, Necrotizing - prevention & control; Enterohepatic Circulation - drug effects; Erythropoiesis; Exposure; Female; Fetus - blood supply; Fetuses; Gene expression; Histology; Infections; Inflammation; Injections, Intralesional; Intestine; intra-uterine infection; Liver; Liver - blood supply; Necrotizing enterocolitis; Newborn babies; Parenchyma; Phytosterols - administration & dosage; Phytosterols - pharmacology; Phytotherapy; plant sterols; Post-Exposure Prophylaxis - methods; Pregnancy; Premature birth; preterm birth; Proteins; Sheep; Sitosterols - administration & dosage; Sitosterols - pharmacology; Software; Sterols; Ureaplasma; Ureaplasma Infections; Ureaplasma parvum; Uterus; Veins & arteries; β-Cyclodextrin; United Kingdom > UK; United States > US; preterm birth; Ureaplasma parvum; liver; plant sterols; intra-uterine infection; chorioamnionitis; sheep; enterohepatic circulation
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12051312

Chorioamnionitis can lead to inflammation and injury of the liver and gut, thereby predisposing patients to adverse outcomes such as necrotizing enterocolitis (NEC). In addition, intestinal bile acids (BAs) accumulation is causally linked to NEC development. Plant sterols are a promising intervention to prevent NEC development, considering their anti-inflammatory properties in the liver. Therefore, we investigated whether an intra-amniotic (IA) (UP) infection affected the liver and enterohepatic circulation (EHC) and evaluated whether an IA administered plant sterol mixture dissolved in β-cyclodextrin exerted prophylactic effects. An ovine chorioamnionitis model was used in which liver inflammation and the EHC were assessed following IA UP exposure in the presence or absence of IA prophylactic plant sterols (a mixture of β-sitosterol and campesterol dissolved in β-cyclodextrin (carrier)) or carrier alone. IA UP exposure caused an inflammatory reaction in the liver, histologically seen as clustered and conflated hepatic erythropoiesis in the parenchyma, which was partially prevented by IA administration of sterol + β-cyclodextrin, or β-cyclodextrin alone. In addition, IA administration of β-cyclodextrin prior to UP caused changes in the expression of several hepatic BAs transporters, without causing alterations in other aspects of the EHC. Thereby, the addition of plant sterols to the carrier β-cyclodextrin did not have additional effects.