Obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland.

BACKGROUND AND OBJECTIVE: Our patient cohort revealed that obesity is strongly associated with steroid-5α reductase type 2 (SRD5A2) promoter methylation and reduced protein expression. The underlying mechanism of prostatic growth in this population is poorly understood. Here we addressed the question of how obesity, inflammation, and steroid hormones affect the development of benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: We used preadipocytes, macrophages, primary human prostatic stromal cells, prostate tissues from high-fat diet-induced obese mice, and 35 prostate specimens that were collected from patients who underwent transurethral resection of the prostate (TURP). RNA was isolated and quantified with RT-PCR. Genome DNA was extracted and SRD5A2 promoter methylation was determined. Sex hormones were determined by high-performance liquid chromatography-tandem mass spectrometry. Protein was extracted and determined by ELISA test. RESULTS: In prostatic tissues with obesity, the levels of inflammatory mediators were elevated. SRD5A2 promoter methylation was promoted, but SRD5A2 expression was inhibited. Inflammatory mediators and saturated fatty acid synergistically regulated aromatase activity. Obesity promoted an androgenic to estrogenic switch in the prostate. CONCLUSIONS: Our findings suggest that obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland, which may serve as an effective strategy for alternative therapies for management of lower urinary tract symptoms associated with BPH in select individuals.

Determination of antioxidant activity of phenolic antioxidants in a Fenton-type reaction system by chemiluminescence assay.

The hydroxyl radical (*OH) has been implicated in various diseases, and it is therefore important to establish efficient methods to screen hydroxyl radical scavengers for antioxidant therapy. In this paper, a simple chemiluminescence assay was established to evaluate the *OH-scavenging capacity of phenolic compounds. This assay took advantage of the transient property of the Fenton reaction and the reaction between luminol and the hydroxyl radical, and effectively avoided the pro-oxidant action of some phenolic compounds. Fifteen phenolic compounds were assessed for their antioxidant activity in the Fenton reaction system, and even in the case of "pro-oxidants" that were excluded from the widely used deoxyribose (DR) assay. Since it overcomes the challenges that the traditional DR assay encounters, our method has promising applicative values: it is low-cost, time-saving, and reliable. It would also be more favorable than electron spin resonance (ESR) and radiolysis technology, which are known to be expensive and not commonly available to those specialized in free radical biology and medicine.

Establishment of a quantitative structure-activity relationship model for evaluating and predicting the protective potentials of phenolic antioxidants on lipid peroxidation.

Antioxidant activities of phenolic compounds have been extensively explored, but the determinant factors underlying their mechanisms of action remain to be elucidated. In the present work, a series of phenolic compounds (hydroxylated connamic, benzoic acid, and polyphenol) were studied for their protection against lipid peroxidation (LPO) in two model experiments, pre-emulsified linoleic acid system and phosphate buffered linolenic acid system. The mechanisms of action as well as activity determinants were investigated by computational chemistry and multiple-linear regression analysis. Upon elucidating the LPO inhibition properties and the relationship between their structural natures and antioxidant activities (SAR), a fairly satisfactory multidescriptor quantitative SAR model was derived, which extended our understanding of LPO inhibition mechanisms and should be valuable in assessing or predicting the anti-LPO activity of phenolic antioxidants.