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.

RETRACTED: Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats

“…In general, antidepressants have been reported to induce profibrotic responses via lysophosphatidic acid signaling [12]. Our data are consistent with the ability of Amitrip to enhance TGF-β release and fibrosis [33]. The positive role of the TGF-β superfamily in mediating wound healing is well-documented and has been reviewed [34].…”

Histological, immunohistochemical and radiographic evaluation of Amitriptyline administration on the periodontium of albino rats (An experimental study)

“…Histological examination of PDL in our study revealed apparently its increased thickness with areas of disorganization and degeneration. These results are in parallel with de Almeida Prado et al, (2012) who found that 20 mg/kg of Amitriptyline increased fibrosis in bladder of infravesical obstruction model in rats. They related this fibrosis to increased collagen deposition.…”

Expression of Toll-Like Receptors in the Animal Model of Bladder Outlet Obstruction

“…This could be explained by the relative short time span of the acute phase of inflammation. In the study by de Almeida Prado et al, a transition from neutrophil (polynuclear) to macrophage (mononuclear) infiltration in the bladder tissues of Wistar rats with BOO was observed between the first and the fourteenth day [ 25 ]. Similarly, Liang et al found macrophages infiltration in the bladder tissues of Sprague Dawley rats with BOO after 4 weeks [ 26 ].…”