Iodine prevents the increase of testosterone-induced oxidative stress in a model of rat prostatic hyperplasia

Abstract

Oxidative stress and inflammation are involved in the development and/or progression of benign prostatic hyperplasia (BPH). Molecular iodine (I₂) induces antiproliferative and apoptotic effects in prostate cancer cells, but it is unknown if I₂ regulates oxidative stress in the normal and/or tumoral prostate. The purpose of this study was to analyze the effects of I₂ and celecoxib (Cxb) on oxidative stress and inflammation in a model of prostatic hyperplasia. Cxb was used as positive control of cyclooxygenase-2 (COX-2) inhibition. Prostatic hyperplasia was induced in male Wistar rats (170g) with testosterone (5mg/kg/week, for three weeks). One week before hyperplasia induction, I₂ (25mg/day/rat) or Cxb (1.25mg/day/rat) was supplied for four weeks in the drinking water. Prostatic hyperplasia was evaluated by histological analysis, DNA content, and/or proliferating cell nuclear antigen (PCNA) expression. Lipoperoxidation (malondialdehyde) and nitrite (NO2^-) levels were analyzed by colorimetric methods, while nitric oxide synthase (NOS), COX, and myeloperoxidase (MPO) enzymes were analyzed using RT-PCR, immunoblotting, and/or enzymatic assays. Levels of 15-F2t-isoprostanes, prostaglandins (PGE₂), leukotrienes (LTB₄), and tumor necrosis factor alpha (TNFα) were measured by ELISA. Control testosterone-treated animals exhibited hyperplasia in the dorsolateral prostate, as well as increments in almost all oxidative parameters except for COX-1, TNFα, or MPO. I₂ and Cxb prevented epithelial hyperplasia (DNA content) and oxidative stress induction generated by testosterone in almost the same intensity, and the minimum I₂ dose required was 2.5mg/rat. The antioxidant capacity of I₂ was also analyzed in a cell-free system, showing that this element inhibited the conversion of nitrate (NO₃^-) to NO₂^-. I₂ did not modify the prostatic oxidative state in testosterone untreated rats. In summary, our data showed that antiproliferative and antioxidant effects of I₂ involve the inhibition of NOS and the COX-2 pathway. Further studies are necessary to analyze the therapeutic and/or adjuvant effects of I₂ with first-line medications used to treat BPH.

Keywords: Hyperplasia; Iodine; Oxidative stress; Prostate.