Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats
One of the organ-specific functions of the liver is the excretion of bilirubin into the bile. Membrane transport of bilirubin from the blood to the liver is not only an orphan function, because there is no link to the protein/gene units that perform this function, but also a poorly characterised fun...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222014330 |
| _version_ | 1811187732313014272 |
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| author | Paola Pelizzo Marco Stebel Nevenka Medic Paola Sist Andreja Vanzo Andrea Anesi Urska Vrhovsek Federica Tramer Sabina Passamonti |
| author_facet | Paola Pelizzo Marco Stebel Nevenka Medic Paola Sist Andreja Vanzo Andrea Anesi Urska Vrhovsek Federica Tramer Sabina Passamonti |
| author_sort | Paola Pelizzo |
| collection | DOAJ |
| description | One of the organ-specific functions of the liver is the excretion of bilirubin into the bile. Membrane transport of bilirubin from the blood to the liver is not only an orphan function, because there is no link to the protein/gene units that perform this function, but also a poorly characterised function. The aim of this study was to investigate the pharmacology of bilirubin uptake in the liver of the female Wistar rat to improve basic knowledge in this neglected area of liver physiology. We treated isolated perfused livers of female rats with repeated single-pass, albumin-free bilirubin boli. We monitored both bilirubin and bilirubin glucuronide in perfusion effluent with a bio-fluorometric assay. We tested the ability of nine molecules known as substrates or inhibitors of sinusoidal membrane transporters to inhibit hepatic uptake of bilirubin. We found that cyanidin 3-glucoside and malvidin 3-glucoside were the only molecules that inhibited bilirubin uptake. These dietary anthocyanins resemble bromosulfophthalein (BSP), a substrate of several sinusoidal membrane transporters. The SLCO-specific substrates estradiol-17 beta-glucuronide, pravastatin, and taurocholate inhibited only bilirubin glucuronide uptake. Cyanidin 3-glucoside and taurocholate acted at physiological concentrations. The SLC22-specific substrates indomethacin and ketoprofen were inactive. We demonstrated the existence of a bilirubin-glucuronide transporter inhibited by bilirubin, a fact reported only once in the literature. The data suggest that bilirubin and bilirubin glucuronide are transported to the liver via pharmacologically distinct membrane transport pathways. Some dietary anthocyanins may physiologically modulate the uptake of bilirubin into the liver. |
| first_indexed | 2024-04-11T14:08:27Z |
| format | Article |
| id | doaj.art-b8ed9ae5cb3844b9ae8191e39e917375 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-11T14:08:27Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-b8ed9ae5cb3844b9ae8191e39e9173752022-12-22T04:19:49ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-01-01157114044Cyanidin 3-glucoside targets a hepatic bilirubin transporter in ratsPaola Pelizzo0Marco Stebel1Nevenka Medic2Paola Sist3Andreja Vanzo4Andrea Anesi5Urska Vrhovsek6Federica Tramer7Sabina Passamonti8Department of Life Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, ItalyDepartment of Life Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, ItalyDepartment of Life Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, ItalyDepartment of Life Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, ItalyDepartment of Fruit Growing, Viticulture and Oenology, Agricultural Institute of Slovenia, Hacquetova ulica 17, SI-1000 Ljubljana, SloveniaFood Quality and Nutrition, Research and Innovation Centre, Edmund Mach Foundation, Via E. Mach 1, 38010 San Michele all'Adige, ItalyFood Quality and Nutrition, Research and Innovation Centre, Edmund Mach Foundation, Via E. Mach 1, 38010 San Michele all'Adige, ItalyDepartment of Life Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, ItalyDepartment of Life Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy; Correspondence to: Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy.One of the organ-specific functions of the liver is the excretion of bilirubin into the bile. Membrane transport of bilirubin from the blood to the liver is not only an orphan function, because there is no link to the protein/gene units that perform this function, but also a poorly characterised function. The aim of this study was to investigate the pharmacology of bilirubin uptake in the liver of the female Wistar rat to improve basic knowledge in this neglected area of liver physiology. We treated isolated perfused livers of female rats with repeated single-pass, albumin-free bilirubin boli. We monitored both bilirubin and bilirubin glucuronide in perfusion effluent with a bio-fluorometric assay. We tested the ability of nine molecules known as substrates or inhibitors of sinusoidal membrane transporters to inhibit hepatic uptake of bilirubin. We found that cyanidin 3-glucoside and malvidin 3-glucoside were the only molecules that inhibited bilirubin uptake. These dietary anthocyanins resemble bromosulfophthalein (BSP), a substrate of several sinusoidal membrane transporters. The SLCO-specific substrates estradiol-17 beta-glucuronide, pravastatin, and taurocholate inhibited only bilirubin glucuronide uptake. Cyanidin 3-glucoside and taurocholate acted at physiological concentrations. The SLC22-specific substrates indomethacin and ketoprofen were inactive. We demonstrated the existence of a bilirubin-glucuronide transporter inhibited by bilirubin, a fact reported only once in the literature. The data suggest that bilirubin and bilirubin glucuronide are transported to the liver via pharmacologically distinct membrane transport pathways. Some dietary anthocyanins may physiologically modulate the uptake of bilirubin into the liver.http://www.sciencedirect.com/science/article/pii/S0753332222014330BilirubinSinusoidal transporterCyanidin-3-O-beta-glucopyranosidePravastatinEstradiol-17 betaglucuronideOrganic anion transporters |
| spellingShingle | Paola Pelizzo Marco Stebel Nevenka Medic Paola Sist Andreja Vanzo Andrea Anesi Urska Vrhovsek Federica Tramer Sabina Passamonti Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats Biomedicine & Pharmacotherapy Bilirubin Sinusoidal transporter Cyanidin-3-O-beta-glucopyranoside Pravastatin Estradiol-17 betaglucuronide Organic anion transporters |
| title | Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats |
| title_full | Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats |
| title_fullStr | Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats |
| title_full_unstemmed | Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats |
| title_short | Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats |
| title_sort | cyanidin 3 glucoside targets a hepatic bilirubin transporter in rats |
| topic | Bilirubin Sinusoidal transporter Cyanidin-3-O-beta-glucopyranoside Pravastatin Estradiol-17 betaglucuronide Organic anion transporters |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222014330 |
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