{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:34:36Z","timestamp":1768505676659,"version":"3.49.0"},"posted":{"date-parts":[[2023,8,13]]},"group-title":"Pharmacology and Toxicology","reference-count":52,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,8,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND AND AIMS<\/jats:title>\n                  <jats:p>Biliary atresia is a fibrosing cholangiopathy affecting neonates that is thought to be caused by a prenatal environmental insult to the bile duct. Biliatresone, a plant toxin with an \u03b1-methylene ketone group, was previously implicated in toxin-induced biliary atresia in Australian livestock, but is found in a limited location and is highly unlikely to be a significant human toxin. We hypothesized that other molecules with \u03b1-methylene ketone groups, some with the potential for significant human exposure, might also be biliary toxins.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>APPROACH AND RESULTS<\/jats:title>\n                  <jats:p>We focused on the family of microcystins, cyclic peptide toxins from blue-green algae that have an \u03b1-methylene ketone group and are found worldwide, particularly during harmful algal blooms. We found that microcystin-RR, but not 6 other microcystins, caused damage to cell spheroids made using cholangiocytes isolated from 2-3-day-old mice, but not from adult mice. We also found that microcystin- RR caused occlusion of extrahepatic bile duct explants from 2-day-old mice, but not 18-day-old mice. Microcystin-RR caused elevated reactive oxygen species in neonatal cholangiocytes, and treatment with N-acetyl cysteine partially prevented microcystin-RR- induced lumen closure, suggesting a role for redox homeostasis in its mechanism of action.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>This study highlights the potential for environmental toxins to cause neonatal biliary disease and identifies microcystin-RR acting via increased redox stress as a possible neonatal bile duct toxin.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.08.09.552661","type":"posted-content","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:30:11Z","timestamp":1691973011000},"source":"Crossref","is-referenced-by-count":2,"title":["Microcystin-RR is a biliary toxin selective for neonatal cholangiocytes"],"prefix":"10.64898","author":[{"given":"Kapish","family":"Gupta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongning","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6988-4102","authenticated-orcid":false,"given":"Rebecca G.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023081615500493000_2023.08.09.552661v1.1","first-page":"646","article-title":"Biliary atresia in French Polynesia. 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