Invited critical reviewBilirubin toxicity to human erythrocytes: A review
Section snippets
Bilirubin and neonatal jaundice
Bilirubin is the principal degradation end product of heme moiety from hemoglobin and other hemoproteins in mammals. Due to its structure, unconjugated bilirubin (UCB) is poorly soluble in aqueous medium (< 70 nM). Therefore, over 99.9% UCB is transported in the blood tightly bound to albumin and biotransformation is required for excretion [1], [2], [3]. Due to the augmented hemolysis and to the immaturity of the mechanisms for bilirubin disposition in the neonatal period, virtually all newborn
Conclusions
In this review, we show that in vitro exposure of human RBC to UCB induces profound disturbances of cell integrity and morphology and that cellular uptake of UCB is enhanced by the presence of the bilirubin-displacing drug, sulfisoxazole. These perturbations increase with the UCB to albumin molar ratio and with acidosis, pointing to diacid UCB as the cytotoxic species and implicating the UCB precipitates in the irreversible mechanisms of cytotoxicity. This late finding was corroborated by the
Acknowledgements
The authors wish to express their appreciation to all the co-authors of the publications, in which findings are described in this review. Studies from the authors' research unit were funded by Fundação para a Ciência e a Tecnologia (Portugal).
References (81)
Bilirubin metabolism and kernicterus
Adv Pediatr
(1997)- et al.
Molecular basis of bilirubin-induced neurotoxicity
Trends Mol Med
(2004) Neonatal jaundice: physiologic variation or pathologic process
Crit Care Nurs Clin North Am
(2004)- et al.
Understanding and preventing severe neonatal hyperbilirubinemia: is bilirubin neurotoxity really a concern in the developed world?
Clin Perinatol
(2004) - et al.
Jaundice in full-term and near-term babies who leave the hospital within 36. The pediatrician's nemesis
Clin Perinatol
(1998) - et al.
Unconjugated bilirubin inhibits in vitro cytotoxic T lymphocyte activity of human lymphocytes
Biochim Biophys Acta
(1996) - et al.
Impairment of DNA synthesis in Gunn rat cerebellum
Brain Res
(1977) - et al.
Cytokine production, glutamate release and cell death in rat cultured astrocytes treated with unconjugated bilirubin and LPS
J Neuroimmunol
(2004) - et al.
Bilirubin-induced erythrocyte membrane cytotoxicity
Exp Mol Pathol
(1981) - et al.
Inhibition of glutamate uptake by unconjugated bilirubin in cultured cortical rat astrocytes: role of concentration and pH
Biochem Biophys Res Commun
(1999)