Bilirubin is a catabolic product of hem, which is an integral part of haemoglobin, myoglobin, cytochrome, catalase and peroxidase. Hem is catalysed to biliverdin through heme-oxygenase, which in turn is reduced to bilirubin by biliverdin reductase, in the cells. In healthy people the total amount of bilirubin in serum is normally between 5 and 17 µM. Bilirubin is a lipophilic molecule which, in blood, is non-covalently bound to the serum protein albumin. Polar complex albumin-bilirubin is made and transported through the blood. In healthy people, approximately 10 nM of unbound or free bilirubin exists in serum; this is, however, in equlibrium with bilirubin bound to albumin. Higher concentrations of bilirubin have a neurotoxic effect in newborns (kernicterus) or in adults with serious liver failure (bilirubin encephalopathy). Some drugs can cause the release of bilirubin through competitive interaction with bilirubin on the albumin binding sites. This can increase the free bilirubin concentration. This thesis demonstrates competition between bilirubin and ibuprofen for the binding site of albumin by employing four different experimental methods. Moreover, we also show that ibuprofen displaced bilirubin from the albumin binding site. We found that ketoprofen (a drug similar to ibuprofen), has the same ability to displace bilirubin from the binding site, as ibuprofen. We designed a model with the potential to implement high-throughput screening for the identification of drugs that interact with bilirubin-albumin binding mechanism. Presently, there is a gap of knowledge in interaction of different drugs to albumin binding sites.
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