Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats

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.本数据集关联于题为《花青素3-葡萄糖苷靶向大鼠肝胆红素转运蛋白》（Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats）的研究论文。本研究针对雌性Wistar大鼠的肝脏胆红素摄取药理学机制展开探究，旨在填补该长期被忽视的肝脏生理学研究领域的基础认知空白。我们对雌性大鼠的离体灌注肝脏进行多次单次弹丸式给药，所用制剂为不含白蛋白的胆红素。我们通过生物荧光测定法监测灌注流出液中的胆红素与胆红素葡萄糖醛酸苷水平。我们测试了9种已知作为血窦膜转运蛋白底物或抑制剂的分子对肝脏胆红素摄取的抑制活性。结果显示，仅花青素3-葡萄糖苷（cyanidin 3-glucoside）与锦葵素3-葡萄糖苷（malvidin 3-glucoside）可抑制胆红素的肝脏摄取。SLCO家族特异性底物雌二醇-17β-葡萄糖苷酸、普伐他汀及牛磺胆酸盐仅能抑制胆红素葡萄糖醛酸苷的摄取。花青素3-葡萄糖苷与牛磺胆酸盐可在生理浓度下发挥作用。SLC22家族特异性底物吲哚美辛与酮洛芬无抑制活性。本研究证实了一种可被胆红素抑制的胆红素葡萄糖醛酸苷转运蛋白的存在，该现象此前仅在一篇学术文献中被报道。实验数据表明，胆红素与胆红素葡萄糖醛酸苷通过药理学特征迥异的细胞膜转运通路被肝脏摄取。部分膳食来源的花青素或可生理性调控肝脏对胆红素的摄取过程。