Toxins and Biliary Atresia

Pack, Michael; Wells, Rebecca G.

doi:10.1002/9781119436812.ch75

Cited by 2 publications

(3 citation statements)

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“…There are multiple known general biliary toxins, as well as natural toxic causes of organ fibrosis, and thus, the role of a biliary toxin in BA would not be surprising [ 15 ]. The toxin biliatresone, a naturally occurring isoflavonoid-related 1,2-diaryl-2-propenone found in Dysphania glomulifera and D. littoralis , has been implicated in BA-like syndrome outbreaks in Australian livestock [ 13 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Environmental Toxin Biliatresone-Induced Biliary Atresia-like Abnormal Cilia and Bile Duct Cell Development of Human Liver Organoids

Hai-Bing,

Sivasankaran,

Ottakandathil

et al. 2024

Toxins

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Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. Biliatresone, a plant toxin, causes BA-like syndrome in some animals, but its relevance in humans is unknown. To validate the hypothesis that biliatresone exposure is a plausible BA disease mechanism in humans, we treated normal human liver organoids with biliatresone and addressed its adverse effects on organoid development, functions and cellular organization. The control organoids (without biliatresone) were well expanded and much bigger than biliatresone-treated organoids. Expression of the cholangiocyte marker CK19 was reduced, while the hepatocyte marker HFN4A was significantly elevated in biliatresone-treated organoids. ZO-1 (a tight junction marker) immunoreactivity was localized at the apical intercellular junctions in control organoids, while it was markedly reduced in biliatresone-treated organoids. Cytoskeleton F-actin was localized at the apical surface of the control organoids, but it was ectopically expressed at the apical and basal sides in biliatresone-treated organoids. Cholangiocytes of control organoids possess primary cilia and elicit cilia mechanosensory function. The number of ciliated cholangiocytes was reduced, and cilia mechanosensory function was hampered in biliatresone-treated organoids. In conclusion, biliatresone induces morphological and developmental changes in human liver organoids resembling those of our previously reported BA organoids, suggesting that environmental toxins could contribute to BA pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Environmental Toxin Biliatresone-Induced Biliary Atresia-like Abnormal Cilia and Bile Duct Cell Development of Human Liver Organoids

Hai-Bing,

Sivasankaran,

Ottakandathil

et al. 2024

Toxins

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“…Recently, a plant isoflavonoid named biliatresone was found to cause a BA-like disease in livestock 4,5,9 . There may be similar toxins in the environment that mimic the effects and properties of biliatresone 10 . In our institutional experience, we noticed significant annual fluctuation in both biliary atresia cases as well as severity of red tide outbreaks in the Southwest Gulf of Mexico (Figure 1) prompting the hypothesis that there could be a relationship between the two phenomena.…”

Section: Introductionmentioning

confidence: 99%

“…In our institutional experience, we noticed significant annual fluctuation in both biliary atresia cases as well as severity of red tide outbreaks in the Southwest Gulf of Mexico (Figure 1) prompting the hypothesis that there could be a relationship between the two phenomena. There have been few studies exploring the association between environmental toxins and development of BA in humans 10 . Red tide blooms, caused by the dinoflagellate Karenia brevis , occur in the late summer and early fall but can last days, weeks or months 11 .…”

Section: Introductionmentioning

confidence: 99%

A Case-Control Study of the Association BetweenKarenia Brevis(Red Tide) and Biliary Atresia

Wyrebek

Fierstein

Wells

et al. 2022

Preprint

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ObjectiveThe study objective was to evaluate the association between maternal Karenia brevis (K. brevis) exposure during pregnancy and the prevalence of biliary atresia (BA) in offspring.Study DesignThis was a hospital-based, case-control study in which cases were infants diagnosed with BA at Johns Hopkins All Childrens Hospital from October 2001 to December 2019. Controls were matched 4:1 by age, randomly selected from healthy infants hospitalized during the study period for common pediatric diagnoses. Infants were excluded if they had congenital anomalies and/or were non-Florida residents. Gestational K. brevis exposure levels (cells/liter) were determined from Florida Fish and Wildlife Conservation Commission exposure data at 10- and 50-mile radii from the maternal zip code of residence. Multivariable conditional logistic regression determined adjusted odds of BA in offspring based on maternal gestational K. brevis exposure.ResultsOf 38 cases and 152 controls, no significant inter-group differences were observed in race/ethnicity, season of birth or coastal residence. Median gestational exposure at the 10-mile radius was 0 cells/liter in both groups. A greater proportion of cases had no K. brevis exposure (63.2%, n = 24) in comparison to controls (37.5%, n = 57; p = .04) at a 10-mile radius. At the 50-mile radius, cases had a peak median exposure at 6 months of gestation compared to controls peak at 9 months. After adjustment for sex, seasonality, race/ethnicity, and coastal residence, there was no significant association between BA and maximum K. brevis exposure per trimester of pregnancy at the 10- or 50-mile radius.ConclusionWe observed no association between gestational K. brevis (cells/liter) exposure at a 10- and 50-mile radius from maternal zip code of residence and BA in offspring.

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Toxins and Biliary Atresia

Cited by 2 publications

References 54 publications

Environmental Toxin Biliatresone-Induced Biliary Atresia-like Abnormal Cilia and Bile Duct Cell Development of Human Liver Organoids

Environmental Toxin Biliatresone-Induced Biliary Atresia-like Abnormal Cilia and Bile Duct Cell Development of Human Liver Organoids

A Case-Control Study of the Association BetweenKarenia Brevis(Red Tide) and Biliary Atresia

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