Korean J Urol.  2014 Nov;55(11):756-763. 10.4111/kju.2014.55.11.756.

Stereological Comparison of the Effects of Pentoxifylline, Captopril, Simvastatin, and Tamoxifen on Kidney and Bladder Structure After Partial Urethral Obstruction in Rats

• Shirazi M
• Soltani MR
• Jahanabadi Z
• Abdollahifar MA
• Tanideh N
• Noorafshan A

• KMID: 2069919
• DOI: http://doi.org/10.4111/kju.2014.55.11.756

Abstract

PURPOSE
Limited studies have shown antifibrotic effects of pentoxifylline, captopril, simvastatin, and tamoxifen. No comparisons are available of the effects of these drugs on prevention of renal and bladder changes in partial urethral obstruction (PUO).
MATERIALS AND METHODS
The rats were divided into six groups (n=7). The sham-operated rats (group I) only underwent laparotomy and did not receive any treatments. The PUO groups (group II-VI) received normal saline (PUO+NS), pentoxifylline (100 mg/kg/d; PUO+PEN), captopril (35 mg/kg/d; PUO+CAP), simvastatin (15 mg/kg/d; PUO+SIM), or tamoxifen (10 mg/kg/d; PUO+TAM) by gavage for 28 days. Then, the volume and/or length of the kidney components (tubules, vessels, and fibrous tissue) and the bladder components (epithelial and muscular layers, fibrous tissue, fibroblast and fibrocyte number) were quantitatively evaluated on the microscopic sections by use of stereological techniques.
RESULTS
The volume of renal and bladder fibrosis was significantly ameliorated in the PUO+PEN group, followed by the PUO+CAP, PUO+SIM, and PUO+TAM groups. Also, the volume and length of the renal tubules and vessels and bladder layers were more significantly protected in the PUO+PEN group, followed by the PUO+CAP, PUO+SIM, and PUO+TAM groups.
CONCLUSIONS
Treatment of PUO with PEN was more effective in the prevention of renal and bladder fibrosis and in the preservation of renal and bladder structures.

Keyword

Captopril; Pentoxifylline; Simvastatin; Tamoxifen; Urethral obstruction

MeSH Terms

Angiotensin-Converting Enzyme Inhibitors/pharmacology
Animals
Captopril/*pharmacology
Disease Models, Animal
Estrogen Antagonists/pharmacology
Free Radical Scavengers/pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
Kidney/*drug effects/pathology
Male
Pentoxifylline/*pharmacology
Rats
Simvastatin/*pharmacology
Tamoxifen/*pharmacology
Urethral Obstruction/*drug therapy
Urinary Bladder Neck Obstruction/*drug therapy
Angiotensin-Converting Enzyme Inhibitors
Captopril
Estrogen Antagonists
Free Radical Scavengers
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pentoxifylline
Simvastatin
Tamoxifen

Figure

• 

  FIG. 1 Micrograph of the kidney in the different groups. (A) Sham-operated animals with normal structure. (B) PUO+normal saline treatment. The normal tubular cells are lost. Fibrous tissue was formed and replaced the tubular tissue. The tubules seemed dilated. (C) PUO+PEN, (D) PUO+CAP, (E) PUO+SIM, (F) PUO+TAM. Heidenhain's AZAN trichrome stain (scale bar, 50 µm). PUO, partial urethral obstruction; PEN, pentoxifylline; CAP, captopril; SIM, simvastatin; TAM, tamoxifen.

• 

  FIG. 2 Micrograph of the bladder in the different groups. (A) Sham-operated animals with normal structure. (B) PUO+ NS, (C) PUO+PEN, (D) PUO+CAP, (E) PUO+SIM, (F) PUO+TAM. PUO without pharmacological treatment showed that more epithelial tissue can be seen. The muscle layer was hypertrophied. Fibrous tissue was increased in the different layers of the bladder. PUO+PEN ameliorated the changes in bladder structure followed by CAP, SIM, and TAM. Heidenhain's AZAN trichrome stain (scale bar, 250 µm). PUO, partial urethral obstruction; PEN, pentoxifylline; CAP, captopril; SIM, simvastatin; TAM, tamoxifen.

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