Atorvastatin attenuates testosterone-induced benign prostatic hyperplasia in rats: role of peroxisome proliferator-activated receptor-γ and cyclo-oxygenase-2

Abstract

Diabetes and obesity have been reported to alter sex steroid hormone metabolism. In this study, an attempt was made to investigate the protective effect of atorvastatin (ATR) in combination with celecoxib (CEL) or pioglitazone (PIO) on testosterone-induced BPH in rats. Male Wistar rats (200-250 g) were randomly divided into nine groups (n = 8) and orally treated as follows for 28 consecutive days: group 1: vehicle control (10 mL/kg); group 2: vehicle testosterone (10 mL/kg); groups 3 - 5: ATR (0.5, 2.5, and 5 mg/kg, respectively); group 6: CEL (20 mg/kg); group 7: PIO (20 mg/kg); and groups 8-9: ATR 0.5 mg/kg, and 15 min later, animals were given CEL (20 mg/kg) or PIO (20 mg/kg), respectively. One hour post-treatment, animals in groups 2-9 were given testosterone propionate (3 mg/kg, s.c.). Twenty-four hours after last treatment on day 28, blood was collected for serum testosterone and prostate-specific antigen (PSA) analysis. Prostate was harvested for biochemical and histological assays. Subcutaneous injection of testosterone increased serum levels of testosterone and PSA which was ameliorated by pretreatments of rat with ATR, celecoxib, or pioglitazone. Similarly, testosterone-induced increase in MDA and reduction in the activity of GSH, superoxide dismutase (SOD), and catalase were attenuated by ATR. Conversely, celecoxib or pioglitazone treatment failed to affect the activity of antioxidant enzymes. The histology of the prostate showed significant improvement in prostatic cells of ATR, celecoxib, or pioglitazone treated. Findings from the study showed that atorvastatin attenuated testosterone-induced BPH. Moreover, synergistic effect was observed when atorvastatin was combined with celecoxib.

Keywords: celecoxib; diabetes; obesity; oxidative stress; pioglitazone.