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

• Published in: Free radical biology & medicine Vol. 115; pp. 298 - 308
• Main Authors: Quintero-García, Michelle, Delgado-González, Evangelina, Sánchez-Tusie, Ana, Vázquez, Mario, Aceves, Carmen, Anguiano, Brenda
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2018
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Celecoxib - therapeutic use; Cyclooxygenase 2 - metabolism; Disease Models, Animal; Humans; Hyperplasia; Iodine; Iodine - therapeutic use; Lipid Peroxidation - drug effects; Male; Oxidative stress; Oxidative Stress - drug effects; Prostate; Prostate - drug effects; Prostate - physiology; Prostatic Hyperplasia - chemically induced; Prostatic Hyperplasia - drug therapy; Rats; Rats, Wistar; Testosterone - administration & dosage; Oxidative stress; Prostate; Hyperplasia; Iodine
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2017.12.014

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.
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•Molecular iodine prevents testosterone-induced hyperplasia on rat prostate.•Molecular iodine supplement does not affect prostate of intact rats.•Iodine exerts effects as comparable with celecoxib.•Iodine mechanisms involve the inhibition of COX and NOS pathways.