Simulation of Bilirubin Detoxification in the Newborn Using an Extracorporeal Bilirubin Oxidase Reactor

Abstract

ABSTRACT. Jaundice, which is characterized by an excessive accumulation of bilirubin in the blood and tissues, occurs in 13% of newborns. The common treatments for neonatal jaundice are phototherapy and blood exchange transfusion. A novel approach using an extracorporeal blood filter containing immobilized bilirubin oxidase was recently proposed to detoxify jaundiced blood, and a prototype device markedly reduced serum bilirubin in genetically jaundiced Gunn rats. The primary toxicologic effect in that study was a 20% reduction in red blood cell count. Using a compartmental model for bilirubin metabolism, a mathematical simulation of the extracorporeal treatment's ability to reduce serum bilirubin levels in jaundiced infants is presented. Using a 10-mL reactor volume containing immobilized bilirubin oxidase, the simulation predicts a 32 to 65% decrease in plasma bilirubin concentration over a 4-h treatment for a 2 kg preterm hyperbilirubinemic newborn. In addition, a new approach to altering support material has essentially eliminated red blood cell lysis in vivo using Gunn rats and in vitro using adult blood. (Pediatr Res 26: [452][453][454][455][456][457] 1989)

Features and applications of bilirubin oxidases

“…The conjugated form results from the transformation of the unconjugated bilirubin in the liver by the enzyme hepatic glucuronyl transferase. The detection of unconjugated bilirubin is more specifically used in newborns where the liver is not mature enough to convert the unconjugated bilirubin to conjugated bilirubin resulting in jaundice affecting~60-80 % of newborns (Goldfinch and Maguire 1988;Kirk 2008; Table 1 Comparison between the kinetics parameters of the BOD from B. pumilus (Durand et al 2012b), B. licheniformis (Koschorreck et al 2008), Bacillus HR03 (Mohammadian et al 2010), B. subtilis (Durao et al 2008), M. verrucaria (Kataoka et al 2005b) and M. oryzae (Durand et al 2012a Mullon et al 1989;Nakamura and Lee 1977). Conjugated bilirubin is known to be a better indicator of liver function and is used in the diagnosis of jaundice and hyperbilirubinemia (Doumas et al 1987(Doumas et al , 1999Kirihigashi et al 2000;Kosaka et al 1987Kosaka et al , 1998Million et al 1988;Mullon and Langer 1987;Perry et al 1986;Soltys et al 1992).…”

Can sunlight replace phototherapy units in the treatment of neonatal jaundice? An in vitro study

“…Chemical compounds have been tested for possible photosensitizing effect to improve the process of bilirubin isomerization, thus reducing treatment time (1,7,9). Hyperbilirubinemia has also been treated by Chinese traditional medicine (14), acupuncture (15), bilirubin oxidase (16,17) and metalloporphyrins (18). However, results are not very encouraging due to the cytotoxicity of some of the chemical agents at different effective concentrations.…”

Peroxisome Proliferator-Activated Receptor (PPARγ) Plays a Protective Role in Cigarette Smoking-Induced Inflammation via AMP-Activated Protein Kinase (AMPK) Signaling

“…Chronic obstructive pulmonary disease (COPD) is a common chronic pulmonary disease, causing 2.9 million deaths every year in the world [ 1 ]. COPD is characterized by persistent respiratory symptoms and airflow limitation, involves obstructive bronchiolitis and emphysema, and may result in respiratory failure and cardiovascular diseases [ 2 ]. The pathogenesis has not been completely elucidated, however, several risk factors have been identified, including smoking.…”