Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats

Pelizzo, Paola; Stebel, Marco; Medic, Nevenka; Sist, Paola; Vanzo, Andreja; Anesi, Andrea; Vrhovšek, Urška; Tramer, Federica; Passamonti, Sabina

doi:10.1016/j.biopha.2022.114044

Cited by 2 publications

(2 citation statements)

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“…Small changes of bilirubinemia are related to a significant decrease in mortality and disease risk [43], but only a few factors are known for causing mild upwards modulation of bilirubinemia, e.g., fasting [44] or weight loss [45], and the interest in finding drugs or natural compounds capable of inducing "iatrogenic Gilbert's syndrome" [46] is still elevated [47]. Precision medicine requires high-performance analytical methods.…”

Section: Domains Of Application In Precision Medicinementioning

confidence: 99%

“…The range of the mean total bilirubinemia values in our study group was 2.35-14.33 µM (HUG assay) or 2.12-16.78 µM (diazo assay), comprising the reference intervals of bilirubin concentrations in human sera [43], as well as the min-max range (1.5-22.6 µM) in the 226 subjects that were analyzed for group difference. 9 Provide an estimate of precision 95% CI for mean of differences from −1.314 to −0.657.…”

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confidence: 99%

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Nanoscale Bilirubin Analysis in Translational Research and Precision Medicine by the Recombinant Protein HUG

Sist,

Tramer,

Bandiera

et al. 2023

IJMS

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Bilirubin is a toxicological biomarker for hemolysis and liver diseases. The current automated diazo method used in clinical chemistry has limited applicability in rodent models and cannot be used in small animals relevant to toxicology, microphysiological systems, cell cultures, and kinetic studies. Here, we present a versatile fluorometric method for nanoscale analysis of bilirubin based on its highly specific binding to the recombinant bifunctional protein HELP–UnaG (HUG). The assay is sensitive (LoQ = 1.1 nM), accurate (4.5% relative standard error), and remarkably robust, allowing analysis at pH 7.4–9.5, T = 25–37 °C, in various buffers, and in the presence of 0.4–4 mg × L−1 serum albumin or 30% DMSO. It allows repeated measurements of bilirubinemia in murine models and small animals, fostering the 3Rs principle. The assay determines bilirubin in human plasma with a relative standard error of 6.7% at values that correlate and agree with the standard diazo method. Furthermore, it detects differences in human bilirubinemia related to sex and UGT1A1 polymorphisms, thus demonstrating its suitability for the uniform assessment of bilirubin at the nanoscale in translational and precision medicine.

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