title: Experimental hemolysis model to study bilirubin encephalopathy in rat brain.
abstract: None of experimental models used to study the toxic effect of unconjugated bilirubin brain accumulation, reproduce the conditions in which the hyperbilirubinemia is a consequence of a hemolytic process, i.e. when important amounts of bilirubin and iron are released. The aim was to develop an animal model to determine the role of bilirubin and iron, in the encephalopathy secondary to a hemolytic disease. Male Wistar rats 7 days old (n=30) were treated with phenylhydrazine as hemolytic at 75 mg/kg body weight intraperitoneally for 2 days and euthanized 24 h after the last dose. Hemoglobin, hematocrit, serum and brain bilirubin, serum iron and lipoperoxidation products, as well as neuronal damage and iron positive staining were evaluated and compared among treated and untreated (n=10) animals. The animals with induced hemolysis showed significant reduction in hemoglobin and hematocrit, increased concentration of total and conjugated bilirubin, as well as of serum iron and lipid peroxidation products. The neuronal damage in treated animals included the presence of altered neurons spread out among normal cells, as well as of iron-staining positive cells. With the use of appropriated pharmacological procedures, the characteristics of the model can be useful to dissect the participation of both bilirubin and iron, on the bilirubin encephalopathy secondary to hemolysis.
authors.affiliation: Laboratorio de Neuroquímica, Instituto Nacional de Pediatría, Mexico.
authors.forename: Gerardo Barragán
authors.initials: GB
authors.lastname: Mejia
authors.forename: Cecilia Ridaura
authors.initials: CR
authors.lastname: Sanz
authors.forename: Marco Martínez
authors.initials: MM
authors.lastname: Avila
authors.forename: Armando Valenzuela
authors.initials: AV
authors.lastname: Peraza
authors.forename: David Calderón
authors.initials: DC
authors.lastname: Guzmán
authors.forename: Hugo Juárez
authors.initials: HJ
authors.lastname: Olguín
authors.forename: Aline Morales
authors.initials: AM
authors.lastname: Ramírez
authors.forename: Edna García
authors.initials: EG
authors.lastname: Cruz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001663:Bilirubin / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006400:Hematocrit / Q000379:methods; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology*; D007501:Iron / Q000097:blood; D007647:Kernicterus / Q000139:chemically induced / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010659:Phenylhydrazines; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006454:Hemoglobins; D010659:Phenylhydrazines; C030299:phenylhydrazine; D007501:Iron; D001663:Bilirubin