Abstract
Neonatal hyperbilirubinemia can cause bilirubin encephalopathy (kernicterus). Spontaneously jaundiced (jj) Gunn rats treated with sulfonamide (sulfa) to displace bilirubin from serum albumin, develop bilirubin encephalopathy and abnormal brainstem auditory evoked potentials (BAEPs) comparable with human newborns. We hypothesized phenylhydrazine (PHZ)-induced hemolysis would significantly elevate total plasma bilirubin (TB) in jj Gunn rat pups and produce BAEP abnormalities similar to those observed after sulfa. PHZ 0, 25, 50, or 75 mg/kg was administered intraperitonealy to 15-d-old jjs. An initial TB was recorded in each animal, and a second recorded 1–4 d postinjection to generate a dose-response curve. After PHZ 75 mg/kg, TB peaked at about 30 mg/dL at 48–72 h. A second group of jjs injected with PHZ (0, 25, 50, or 75 mg/kg) and nonjaundiced controls given PHZ 75 mg/kg had HCT and TB at baseline, and HCT, TB, and BAEPs recorded at 48 h. BAEP wave II and III amplitudes decreased, and I–II and I–III interwave intervals increased indicating abnormal central (brainstem) auditory function. PHZ-induced hemolysis in jaundiced Gunn rat pups produces sufficiently elevated TB levels to produce bilirubin encephalopathy. This new model may be a more clinically relevant experimental model of kernicterus- and bilirubin-induced neurologic disorders.
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Abbreviations
- BAEPs:
-
brainstem auditory evoked potentials
- BIND:
-
bilirubin-induced neurological disorders
- HCT:
-
hematocrit
- IWI:
-
interwave interval
- Jj:
-
homozygous jaundiced Gunn rat
- Nj:
-
heterozygous nonjaundiced Gunn rat
- PHZ:
-
phenylhydrazine
- Sulfa:
-
sulfadimethoxine
- TB:
-
total plasma bilirubin
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Acknowledgements
We thank Drs. Claudio Tiribelli, J. Donald Ostrow, and Dean Cekic for suggesting the use of PHZ in our model.
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This research was supported by N.I.H. R01 grants DC000369 and NS04715 (to S.M.S.).
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Rice, A., Shapiro, S. A New Animal Model of Hemolytic Hyperbilirubinemia-Induced Bilirubin Encephalopathy (Kernicterus). Pediatr Res 64, 265–269 (2008). https://doi.org/10.1203/PDR.0b013e31817d9be0
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DOI: https://doi.org/10.1203/PDR.0b013e31817d9be0
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