In vitro permeability and metabolic stability of bile pigments and the effects of hydrophilic and lipophilic modifcation of biliverdin

Article

Bulmer, Andrew C., Blanchfield, Joanne T., Coombes, Jeff S. and Toth, Istvan. 2008. "In vitro permeability and metabolic stability of bile pigments and the effects of hydrophilic and lipophilic modifcation of biliverdin." Bioorganic and Medicinal Chemistry. 16 (7), pp. 3616-3625. https://doi.org/10.1016/j.bmc.2008.02.2008
Article Title

In vitro permeability and metabolic stability of bile pigments and the effects of hydrophilic and lipophilic modifcation of biliverdin

ERA Journal ID1565
Article CategoryArticle
AuthorsBulmer, Andrew C. (Author), Blanchfield, Joanne T. (Author), Coombes, Jeff S. (Author) and Toth, Istvan (Author)
Journal TitleBioorganic and Medicinal Chemistry
Journal Citation16 (7), pp. 3616-3625
Number of Pages10
Year2008
Place of PublicationUnited Kingdom
ISSN0968-0896
1464-3391
Digital Object Identifier (DOI)https://doi.org/10.1016/j.bmc.2008.02.2008
Abstract

Bile pigments, including bilirubin and biliverdin are tetrapyrrolic, dicarboxylic acids capable of forming conjugates at their propionic acid groups via ester or amide bonds. They possess substantial antioxidant and anti-mutagenic activities and therefore their intestinal absorption might influence the development of cardiovascular disease and cancer. The aim of this study was to investigate whether altering the physico-chemical properties of bile pigments would improve their permeability in an in vitro assay of absorption. Native and synthetically modified bile pigments were tested for gastrointestinal permeability and metabolic stability
using the Caco-2 cell line. In addition, a gross measure of their toxic effects was tested in a red blood cell co-incubation assay.
The apparent permeability of unconjugated bilirubin (1), bilirubin ditaurate (2) and biliverdin (3) through Caco-2 cell monolayers was determined to be 10.4 ± 1.2 · 10 -7, 35.2 ± 3.4 · 10 -7 and 37.0 ± 1.6 · 10 -7 cm/s (mean ± SD), respectively, while biliverdin diglucosamine (4), and biliverdin dioctylamine (5) were impermeable. Unconjugated bilirubin, biliverdin, bilirubin ditaurate and biliverdin
diglucosamine did not decompose when incubated in Caco-2 cell homogenates, whereas biliverdin dioctylamine decomposed
over time. Only unconjugated bilirubin showed toxicity towards red blood cells (P1000 lM), an effect that was abolished by the addition of 40 g/L serum albumin. The data presented here suggest that bile pigments are absorbed across the Caco-2 cell monolayer and that conjugation of biliverdin to hydrophilic or lipophilic moieties decreases their absorption and can reduce their metabolic stability.
In summary, exogenous bilirubin and biliverdin supplements could be absorbed across the intestinal epithelium in vivo and potentially increase circulating concentrations of these antioxidant compounds.

Keywordsunconjugated bilirubin; bilirubin ditaurate; amide conjugate; caco-2 cell; absorption; stability; toxicity
ANZSRC Field of Research 2020420702. Exercise physiology
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Byline AffiliationsUniversity of Queensland
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