Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats

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Data associated to the article "Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats". We investigates 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. 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.

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To reproduce these data, refer to "Protocol for the study of hepatic bilirubin uptake in the isolated perfused rat liver", by M. Stebel, N. Medic, P. Pelizzo, P. Sist, F. Tramer, S. Passamonti, 2021. Available in Protocol Exchange. Go to: https://doi.org/10.21203/rs.3.pex-1698/v1.

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