Evidence map›Paper›PMID 39687604›Full record

ArticleJHEP reports : innovation in hepatology2025

Microcystin-RR is a biliary toxin selective for neonatal extrahepatic cholangiocytes.

Kapish Gupta, Dongning Chen, Rebecca G Wells

Abstract read
In one paragraph

Article in JHEP reports : innovation in hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Biliary atresia.Nature reviews. Disease primers · 2024
    Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Kapish GuptaDivision of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dongning ChenDivision of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Rebecca G WellsDivision of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3M
TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI REBECCA G WELLS · 1997 to 2026
$32.5M
Injury, Progression, and Fibrosis of the Extrahepatic Bile DuctR01DK119290 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI REBECCA G WELLS · 2019 to 2026
$2.9M
NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK119290NIEHS NIH HHS P30 ES013508
6 · The paper itself

Abstract

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 ( Conclusions: We identified MC-RR as a selective neonatal extrahepatic cholangiocyte toxin and suggest that it acts by increasing redox stress. Impact and implications: The plant toxin biliatresone causes a biliary atresia-like disease in livestock and vertebrate animal model systems. We tested the widespread blue-green algal toxin, microcystin-RR, another highly electrophilic unsaturated carbonyl compound that is released during harmful algal blooms, and found that it was also a biliary toxin with specificity for neonatal extrahepatic cholangiocytes. This work should drive further animal studies and, ultimately, studies to determine whether human exposure to microcystin-RR causes biliary atresia.

Indexed as

Algal toxinsBile ductBiliary atresiaGlutathione and oxidative stressHarmful algal bloom

Identifiers

PMID39687604
PMCPMC11648759

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.