title: Effect of two antiandrogens as protectors of prostate and brain in a Huntington's animal model.
abstract: The purpose of this work is to know the effect of flutamide and a novel synthetic steroid 3β-p-Iodobenzoyloxypregnan-4,16- diene-6,20-dione (IBP) on the levels of dopamine, 5-HIAA (5-hydroxyindole acetic acid), and some oxidative stress markers in animal model with Huntington disease. Thirty male Wistar rats divided in groups of 6 animals each were subjected to the following treatment: group A, 3-nitro propionic acid (3-NPA, as inducer of Huntington); group B, flutamide; group C, 3-NPA + flutamide; group D, IBP; and group E, 3-NPA + IBP. Treatment scheme for all groups were at 4 mg/kg/day administered intraperitoneally. The measurement of haemoglobin was carried out from blood while the concentrations of ATPase, 5α-reductase, reduced glutathione (GSH), calcium, H2O2, 5-HIAA, and dopamine were determined from brain and prostate tissues using validated methods. The results depicted a significant decrease of dopamine and GSH in cerebellum/Medulla oblongata of animals treated with IBP. The prostate gland of the same group of treatment also showed a significant decrease in the concentrations of TBARS, H2O2, and total ATPase. In hemispheres of groups D and E, dopamine, H2O2, and total ATPase decreased significantly while in prostate, hemispheres, and cerebellum/Medulla oblongata of groups B and C; calcium, 5α-reductase, ATPase, H2O2, and TBARS were found to witness a significant decrease. Results showed an antiandrogenic activity of flutamide, while the novel steroid IBP showed neuroprotective properties by changes on oxidative stress biomarkers as critical pathways leading to prostate and brain degeneration. Probably steroid homeostasis disequilibrium could have led to alterations in dopamine metabolism GSH in Huntington's disease animal models.
authors.forename: David Calderon
authors.initials: DC
authors.lastname: Guzman
authors.forename: Eugene
authors.initials: E
authors.lastname: Bratoeff
authors.forename: Alejandra Chavez
authors.initials: AC
authors.lastname: Riveros
authors.forename: Norma Osnaya
authors.initials: NO
authors.lastname: Brizuela
authors.forename: Gerardo Barragan
authors.initials: GB
authors.lastname: Mejia
authors.forename: Ernestina Hernandez
authors.initials: EH
authors.lastname: Garcia
authors.forename: Hugo Juarez
authors.initials: HJ
authors.lastname: Olguin
authors.affiliation: Laboratorio de Farmacologia, Instituto Nacional de Pediatria, Av Iman #1, 3er piso, Col Cuicuilco, CP 04530, Mexico City, Mexico. juarezol@yahoo.com.
authors.forename: Edna Garcia
authors.initials: EG
authors.lastname: Cruz
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004394:Dydrogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005485:Flutamide / Q000494:pharmacology*; D006816:Huntington Disease / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007463:Iodobenzoates / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: C000599941:3-p-iodobenzoyloxypregnan-4,16-diene-6,20-dione; D000726:Androgen Antagonists; D015415:Biomarkers; D007463:Iodobenzoates; D018696:Neuroprotective Agents; D006897:Hydroxyindoleacetic Acid; D005485:Flutamide; D004394:Dydrogesterone; D004298:Dopamine