Effect of two Antiandrogens as Protectors of Prostate and Brain in a Huntington`s Animal Model

Author(s):

David Calderon Guzman, Eugene Bratoeff, Alejandra Chavez Riveros, Norma Osnaya Brizuela, Gerardo Barragan Mejia, Ernestina Hernandez Garcia, Hugo Juarez Olguin and Edna Garcia Cruz   Pages 1293 - 1301 ( 9 )

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.

Keywords:

Brain, oxidative biomarkers, prostate, rat, synthetic steroid.

Affiliation:

, , , , , , , Laboratorio de Farmacologia, Instituto Nacional de Pediatria, Av Iman #1, 3er piso, Col Cuicuilco, CP 04530, Mexico City, Mexico.

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