Autor: |
Kapish Gupta, Dongning Chen, Rebecca G. Wells |
Jazyk: |
angličtina |
Rok vydání: |
2025 |
Předmět: |
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Zdroj: |
JHEP Reports, Vol 7, Iss 1, Pp 101218- (2025) |
Druh dokumentu: |
article |
ISSN: |
2589-5559 |
DOI: |
10.1016/j.jhepr.2024.101218 |
Popis: |
Background & Aims: Biliary atresia is a fibrosing cholangiopathy affecting neonates that is thought to result from a prenatal environmental insult to the bile duct. Biliatresone, a plant toxin with an α-methylene ketone group, was previously implicated in biliary atresia in Australian livestock, but is found in a limited location and is unlikely to be a significant human toxin. We hypothesized that other unsaturated carbonyl compounds, some with the potential for significant human exposure, might also be biliary toxins. Methods: We focused on the family of microcystins, cyclic peptide toxins from blue-green algae that are found worldwide, particularly during harmful algal blooms. We used primary extrahepatic cholangiocyte spheroids and extrahepatic bile duct explants from both neonatal [a total of 86 postnatal day (P) 2 mouse pups and 18 P2 rat pups (n = 8–10 per condition for both species)] and adult rodents [a total of 31 P15–18 mice (n = 10 or 11 per condition)] to study the biliary toxicity of microcystins and potential mechanisms involved. Results: Results showed that 400 nM microcystin (MC)-RR, but not six other microcystins or the related algal toxin nodularin, caused >80% lumen closure in cell spheroids made from extrahepatic cholangiocytes isolated from 2–3-day-old mice (p |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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