Role of PPAR-α agonist fenofibrate in the treatment of induced benign prostatic hyperplasia with dysplastic changes in rats.

Abstract

Nearly all men who reach average life expectancy have prostate disease. The most common is benign prostatic hyperplasia (BPH). Peroxisome proliferator-activated receptor alpha (PPARα) had protective effect in different models, but still, there are no studies explain its role in BPH. So that we investigated the effect of fenofibrate (FEN) on induced BPH by testosterone propionate (TP) (3mg/kg/day for 4weeks) subcutaneous injection followed by FEN (300mg/kg/day) was given orally for 4weeks. We measured prostate weights changes, prostatic tissue superoxide dismutase (SOD), and malondialdehyde (MDA) levels. Prostate-specific antigen (PSA), dihydrotestosterone (DHT), and total antioxidant capacity (TAC) in serum were determined. The mRNA gene expressions of proliferating cell nuclear antigen (PCNA), PPARα, and glutathione peroxidase (GPx) in prostatic tissue were also measured by quantitative real-time polymerase chain reaction. In addition, the histopathological changes and activated caspase3 immunoexpression were evaluated. Our results showed that TP succeeded in induction of BPH, which was detected by significant increase in prostate weights, prostatic tissue MDA, serum levels of DHT, PSA, and mRNA gene expression of PCNA but significant decrease in PPARα and GPx gene expression. Moreover, TAC in serum and SOD level in prostate tissue decreased. The histopathological examination showed typical changes of BPH with dysplastic changes with marked decrease in activated caspase3 immunoexpression indicating marked suppression of the apoptotic process. FEN significantly improved all disturbed parameters of BPH model. Moreover, there are no dysplastic changes with co-administration of FEN to BPH induced group.