title: Neuroprotective Effect of Erythropoietin on Phenylhydrazine-Induced Hemolytic Hyperbilirubinemia in Neonatal Rats.
abstract: Neonatal unconjugated hyperbilirubinemia might cause severe bilirubin neurotoxicity in especially hemolytic conditions. The study aimed to elucidate the potential neuroprotective effects of erythropoietin (EPO) in hemolysis-induced hyperbilirubinemia. In newborn rats, hyperbilirubinemia secondary to hemolysis was induced by injecting with phenylhydrazine hydrochloride (PHZ) and rats were injected with either vehicle or EPO. At 54th hour of the PHZ injection, rats were decapitated. Serum levels of TNF-α, IL-1β, IL-10, brain-derived neurotrophic factor (BDNF) and S100-B and brain malondialdehyde, glutathione levels and myeloperoxidase activities were measured. TUNEL staining and NF-κB expression were evaluated. As compared to control pups, in vehicle-treated PHZ group, TNF-α and IL-1β levels, malondialdehyde level and myeloperoxidase activity were increased with concomitant decreases in IL-10 and glutathione. All EPO regimens reversed PHZ-induced alterations in IL-10, TNF-α, malondialdehyde and glutathione levels. Three-day-treatment abolished increases in myeloperoxidase activity and IL-1β levels, while BDNF and S100-B were elevated. Increased TUNEL (+) cells and NF-κB expressions in the brain of PHZ group were reduced in the 3-day-treated group. EPO exerted anti-inflammatory effects on PHZ-induced neural damage in newborn rats, while the neuroprotection was more obvious when the treatments were repeated successively. The results suggest that EPO treatment may have a therapeutic potential in supporting neuroplasticity in the hyperbilirubinemic neonates.
authors.affiliation: Department of Paediatrics, Division of Neonatology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Asli
authors.initials: A
authors.lastname: Memisoglu
authors.affiliation: Department of Physiology, Acibadem University School of Medicine, Istanbul, Turkey.
authors.forename: Meltem
authors.initials: M
authors.lastname: Kolgazi
authors.affiliation: Department of Paediatrics, Division of Neonatology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Akan
authors.initials: A
authors.lastname: Yaman
authors.affiliation: Department of Physiology, Marmara University School of Medicine, Basibüyük Mah. Maltepe Basibüyük Yolu No. 9/1, Maltepe, 34854, Istanbul, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Bahadir
authors.affiliation: Department of Histology and Embryology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Sirvanci
authors.affiliation: Department of Physiology, Marmara University School of Medicine, Basibüyük Mah. Maltepe Basibüyük Yolu No. 9/1, Maltepe, 34854, Istanbul, Turkey. byegen@marmara.edu.tr.
authors.forename: Berrak Ç
authors.initials: BÇ
authors.lastname: Yeğen
authors.affiliation: Department of Paediatrics, Division of Neonatology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Eren
authors.initials: E
authors.lastname: Ozek
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006461:Hemolysis / Q000187:drug effects* / Q000502:physiology; D006932:Hyperbilirubinemia / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010659:Phenylhydrazines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D010659:Phenylhydrazines; C030299:phenylhydrazine; D004921:Erythropoietin
keywords: Erythropoietin; Hemolysis; Hyperbilirubinemia; Neonate; Neuroprotective