Pharmacokinetics of bilirubin-10-sulfonate and biliverdin in the rat

Shiels, Ryan; Hewage, Wenu; Vidimce, Josif; Pearson, Andrew G.; Grant, Gary; Wagner, Karl‐Heinz; Bulmer, Andrew Cameron

doi:10.1016/j.ejps.2020.105684

Cited by 7 publications

(2 citation statements)

References 28 publications

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“…The low p K a * value of bilirubin-10-sulfonate seems to be due to its high polarity caused by the sulfonate anion, probably resulting in a p K a * value that is close to that of short chain carboxylic acids 19 . The difference in p K a * values of bilirubin-10-sulfonate and UCB may explain the different biological behavior of bilirubin-10-sulfonate with surprisingly strong intraperitoneal absorption and intravascular retention after intravenous or intraperitoneal administration, and little absorption after intraduodenal administration 29 .…”

Section: Discussionmentioning

confidence: 99%

Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin

Čepa

Dejmková

Lešetický

et al. 2021

Sci Rep

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Unconjugated bilirubin (UCB) is the end-product of heme catabolism in the intravascular compartment. Although beneficial for human health when mildly elevated in the body, when present at greater than a critical threshold concentration, UCB exerts toxic effects that are related to its physico-chemical properties, particularly affecting the central nervous system. The aim of the present study was to characterize bilirubin-10-sulfonate (ranarubin), a naturally occurring bile pigment, including determination of its mixed acidity constants (pKa*). Thanks to the presence of the sulfonic acid moiety, this compound is more polar compared to UCB, which might theoretically solve the problem with an accurate determination of the UCB pKa* values of its propionic acid carboxylic groups. Bilirubin-10-sulfonate was synthesized by modification of a previously described procedure; and its properties were studied by mass spectrometry (MS), nuclear magnetic resonance (NMR), infrared (IR), and circular dichroism (CD) spectroscopy. Determination of pKa* values of bilirubin-10-sulfonate and UCB was performed by capillary electrophoresis with low pigment concentrations in polar buffers. The identity of the synthesized bilirubin-10-sulfonate was confirmed by MS, and the pigment was further characterized by NMR, IR, and CD spectroscopy. The pKa values of carboxylic acid moieties of bilirubin-10-sulfonate were determined to be 5.02, whereas those of UCB were determined to be 9.01. The physico-chemical properties of bilirubin-10-sulfonate were partially characterized with low pKa* values compared to those of UCB, indicating that bilirubin-10-sulfonate cannot be used as a surrogate pigment for UCB chemical studies. In addition, using a different methodological approach, the pKa* values of UCB were found to be in a mildly alkaline region, confirming the conclusions of a recent critical re-evaluation of this specific issue.

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Section: Discussionmentioning

confidence: 99%

Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid–base behavior with unconjugated bilirubin

Čepa

Dejmková

Lešetický

et al. 2021

Sci Rep

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“…The preparations were intraduodenally (i.d.) administered to avoid damage from acidic environment in stomach 20 , 21 . In brief, the rats were anesthetized with 0.3 g/kg chloral hydrate via intraperitoneal injection; following remove of the abdominal hair, a 1-cm incision was made below xiphoid process; a suture was tied gently ∼3 cm distal to the pylorus around the duodenum, preventing the dose from flowing back into the stomach; each preparation at a dose equivalent to 10 mg/kg of PTX was injected 8 cm distal to the pylorus; subsequently, the injection site was sealed by a drop of super glue (Compont Medical Equipment Co., Ltd., Beijing, China), while the suture was removed 3 min later; the abdomen was carefully sutured; at predetermined intervals, 500 μL blood was collected from the eye socket.…”

Section: Methodsmentioning

confidence: 99%