Antioxidant and Cytotoxic Effects of Bilirubin on Neonatal Erythrocytes
- 1 March 1999
- journal article
- Published by Springer Nature in Pediatric Research
- Vol. 45 (3), 355-362
- https://doi.org/10.1203/00006450-199903000-00011
Abstract
Bilirubin, the breakdown product of heme from erythrocytes, accumulates in the neonate in the first days of life. In recent years, the antioxidant properties of bilirubin have been demonstrated in vitro and in vivo, yet it is clear that bilirubin can be toxic to cells. To study the range in which bilirubin exerts its beneficial effect, we used erythrocytes derived from cord blood and incubated them with 0-60 mg/dL bilirubin combined with 3 g/dL BSA (bilirubin/BSA) to mimic physiologic and pathologic conditions. Oxidative stress was induced by incubating the erythrocytes with a solution of 0.6 mM H2O2 and 0.15 M CuSO4 to generate hydroxyl radical mediated injury. The loss of fluorescence of cis-parinaric acid and the degree of protein oxidation of erythrocyte membranes were assessed. Additionally, we determined erythrocyte membrane integrity, glucose-6 phosphate dehydrogenase activity, and adenosine triphosphatase activity before and after incubation with bilirubin/BSA. Incubation with bilirubin/BSA at concentrations up to 60 mg/dL and a bilirubin/BSA molar ratio of two was associated with dose-dependent protection of erythrocytes against lipid peroxidation. However, concentrations of bilirubin equal to or exceeding 30 mg/dL and a bilirubin:BSA ratio of one were associated with increased protein oxidation, decreased erythrocyte glucose-6 phosphate dehydrogenase and adenosine triphosphatase activity, and altered cell membrane integrity. We conclude that bilirubin, at physiologic concentrations, protects neonatal red blood cells against oxidative stress in the presence of physiologic concentrations of BSA but that bilirubin concentrations of 30 mg/dL or higher and a bilirubin:BSA ratio of greater than one are associated with significant cytotoxicity.Keywords
This publication has 38 references indexed in Scilit:
- On the Acid Dissociation Constants of Bilirubin and BiliverdinPublished by Elsevier ,1996
- Glucose-6-phosphate dehydrogenase deficiency and carboxyhemoglobin concentrations associated with bilirubin-related morbidity and death in Nigerian infantsThe Journal of Pediatrics, 1995
- Differential susceptibility of plasma proteins to oxidative modification: Examination by western blot immunoassayFree Radical Biology & Medicine, 1994
- Bilirubin and ascorbate antioxidant activity in neonatal plasmaFEBS Letters, 1994
- Bilirubin attenuates radical‐mediated damage to serum albuminFEBS Letters, 1993
- Decreased erythrocyte Na+, K+-ATPase activity associated with cellular potassium loss in extremely low birth weight infants with nonoliguric hyperkalemiaThe Journal of Pediatrics, 1993
- Brainstem Auditory Evoked Potentials in Icteric Fullterm Newborns: Alterations After Exchange TransfusionNeuropediatrics, 1990
- Parinaric acid as a sensitive fluorescent probe for the determination of lipid peroxidationBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1987
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976
- Control of blood haemoglobin determinations by a simple effective methodJournal of Clinical Pathology, 1962