Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring : Evidence for a spectrum of neonatal injury
Copyright: © 2024 Gupta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
Biliary atresia is a neonatal disease characterized by damage, inflammation, and fibrosis of the liver and bile ducts and by abnormal bile metabolism. It likely results from a prenatal environmental exposure that spares the mother and affects the fetus. Our aim was to develop a model of fetal injury by exposing pregnant mice to low-dose biliatresone, a plant toxin implicated in biliary atresia in livestock, and then to determine whether there was a hepatobiliary phenotype in their pups. Pregnant mice were treated orally with 15 mg/kg/d biliatresone for 2 days. Histology of the liver and bile ducts, serum bile acids, and liver immune cells of pups from treated mothers were analyzed at P5 and P21. Pups had no evidence of histological liver or bile duct injury or fibrosis at either timepoint. In addition, growth was normal. However, serum levels of glycocholic acid were elevated at P5, suggesting altered bile metabolism, and the serum bile acid profile became increasingly abnormal through P21, with enhanced glycine conjugation of bile acids. There was also immune cell activation observed in the liver at P21. These results suggest that prenatal exposure to low doses of an environmental toxin can cause subclinical disease including liver inflammation and aberrant bile metabolism even in the absence of histological changes. This finding suggests a wide potential spectrum of disease after fetal biliary injury.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
PloS one - 19(2024), 4 vom: 01., Seite e0301824 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gupta, Kapish [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Benzodioxoles |
|---|
| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 08.04.2024 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.1371/journal.pone.0301824 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370681541 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370681541 | ||
| 003 | DE-627 | ||
| 005 | 20240408233115.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240406s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.pone.0301824 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1369.xml |
| 035 | |a (DE-627)NLM370681541 | ||
| 035 | |a (NLM)38578745 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gupta, Kapish |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring |b Evidence for a spectrum of neonatal injury |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.04.2024 | ||
| 500 | |a Date Revised 08.04.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright: © 2024 Gupta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
| 520 | |a Biliary atresia is a neonatal disease characterized by damage, inflammation, and fibrosis of the liver and bile ducts and by abnormal bile metabolism. It likely results from a prenatal environmental exposure that spares the mother and affects the fetus. Our aim was to develop a model of fetal injury by exposing pregnant mice to low-dose biliatresone, a plant toxin implicated in biliary atresia in livestock, and then to determine whether there was a hepatobiliary phenotype in their pups. Pregnant mice were treated orally with 15 mg/kg/d biliatresone for 2 days. Histology of the liver and bile ducts, serum bile acids, and liver immune cells of pups from treated mothers were analyzed at P5 and P21. Pups had no evidence of histological liver or bile duct injury or fibrosis at either timepoint. In addition, growth was normal. However, serum levels of glycocholic acid were elevated at P5, suggesting altered bile metabolism, and the serum bile acid profile became increasingly abnormal through P21, with enhanced glycine conjugation of bile acids. There was also immune cell activation observed in the liver at P21. These results suggest that prenatal exposure to low doses of an environmental toxin can cause subclinical disease including liver inflammation and aberrant bile metabolism even in the absence of histological changes. This finding suggests a wide potential spectrum of disease after fetal biliary injury | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a biliatresone |2 NLM | |
| 650 | 7 | |a Bile Acids and Salts |2 NLM | |
| 650 | 7 | |a Benzodioxoles |2 NLM | |
| 700 | 1 | |a Xu, Jimmy P |e verfasserin |4 aut | |
| 700 | 1 | |a Diamond, Tamir |e verfasserin |4 aut | |
| 700 | 1 | |a de Jong, Iris E M |e verfasserin |4 aut | |
| 700 | 1 | |a Glass, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Llewellyn, Jessica |e verfasserin |4 aut | |
| 700 | 1 | |a Theise, Neil D |e verfasserin |4 aut | |
| 700 | 1 | |a Waisbourd-Zinman, Orith |e verfasserin |4 aut | |
| 700 | 1 | |a Winkler, Jeffrey D |e verfasserin |4 aut | |
| 700 | 1 | |a Behrens, Edward M |e verfasserin |4 aut | |
| 700 | 1 | |a Mesaros, Clementina |e verfasserin |4 aut | |
| 700 | 1 | |a Wells, Rebecca G |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t PloS one |d 2006 |g 19(2024), 4 vom: 01., Seite e0301824 |w (DE-627)NLM167327399 |x 1932-6203 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2024 |g number:4 |g day:01 |g pages:e0301824 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.pone.0301824 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2024 |e 4 |b 01 |h e0301824 | ||