title: Amitriptyline aggravates the fibrosis process in a rat model of infravesical obstruction.
abstract: Infravesical obstruction (IVO) secondary to benign prostatic hypertrophy can affect up to 50% of men over 50 years old and may cause serious and irreversible alterations throughout the urinary tract, especially in the bladder. Therapeutic approaches are currently limited. Amitriptyline has recently been described as an analgesic, anti-inflammatory and myorelaxant in some experimental models. The objective of this study was to investigate the effects of amitriptyline hydrochloride on the process of fibrosis in a bladder outlet obstruction model in rats. Male Wistar rats were subjected to IVO and studied at intervals of 1 and 14 days postprocedure. The rats were randomly divided into five groups: sham, IVO1-T, IVO1-NT, IVO14-T and IVO14-NT. Bladder tissue was processed for histopathology, immunohistochemistry and RT-PCR. The IVO14 groups presented bladder fibrosis, smooth muscle cell hypertrophy and bladder wall thickening. The IVO14-T group demonstrated a higher intensity of fibrosis, higher macrophage infiltration rate and higher gene expression of Transforming growth factor (TGF) Tgf-β1. Thus this data shows that in this experimental mode amitriptyline had an amplifying effect on the process of fibrosis as a whole.
authors.affiliation: Department of Pathology, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Patrícia S
authors.initials: PS
authors.lastname: de Almeida Prado
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Soares
authors.forename: Flávio O
authors.initials: FO
authors.lastname: Lima
authors.forename: Nestor
authors.initials: N
authors.lastname: Schor
authors.forename: Vicente P C
authors.initials: VP
authors.lastname: Teixeira
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001748:Urinary Bladder Neck Obstruction / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D053773:Transforming Growth Factor beta1; D000639:Amitriptyline