Abstract
Background:
Hazardous levels of bilirubin produce oxidative stress in vitro and may play a role in the genesis of bilirubin-induced neurologic dysfunction (BIND). We hypothesized that the antioxidants taurourosdeoxycholic acid (TUDCA), 12S-hydroxy-1,12-pyrazolinominocycline (PMIN), and minocycline (MNC) inhibit oxidative stress and block BIND in hyperbilirubinemic j/j Gunn rat pups that were given sulfadimethoxine to induce bilirubin encephalopathy.
Methods:
At peak postnatal hyperbilirubinemia, j/j Gunn rat pups were dosed with sulfadimethoxine to induce bilirubin encephalopathy. Pups were given TUDCA, PMIN, MNC, or vehicle pretreatment (15 min before sulfadimethoxine). After 24 h, BIND was scored by using a rating scale of neurobehavior and cerebellar tissue 4-hydroxynonenal and protein carbonyl dinitrophenyl content were determined. Nonjaundiced heterozygous N/j pups served as controls.
Results:
Administration of sulfadimethoxine induced BIND and lipid peroxidation but not protein oxidation in hyperbilirubinemic j/j pups. TUDCA, PMIN, and MNC each reduced lipid peroxidation to basal levels observed in nonjaundiced N/j controls, but only MNC prevented BIND.
Conclusion:
These findings show that lipid peroxidation inhibition alone is not sufficient to prevent BIND. We speculate that the neuroprotective efficacy of MNC against BIND involves action(s) independent of, or in addition to, its antioxidant effects.
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Acknowledgements
PMIN was provided to the project by Yasuo Konishi and Jean-Manuel Cloarec of the Biotechnology Research Institute, National Research Council Canada, Montreal, Quebec, Canada.
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Daood, M., Hoyson, M. & Watchko, J. Lipid peroxidation is not the primary mechanism of bilirubin-induced neurologic dysfunction in jaundiced Gunn rat pups. Pediatr Res 72, 455–459 (2012). https://doi.org/10.1038/pr.2012.111
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DOI: https://doi.org/10.1038/pr.2012.111
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