Effects of a co-micronized composite containing palmitoylethanolamide and polydatin in an experimental model of benign prostatic hyperplasia

Toxicol Appl Pharmacol. 2017 Aug 15:329:231-240. doi: 10.1016/j.taap.2017.06.005. Epub 2017 Jun 10.

Abstract

Palmitoylethanolamide (PEA), a fatty acid amide-signaling molecule has well-known anti-inflammatory and neuroprotective effects. Nevertheless, PEA does not possess the ability to prevent free radicals formation. Polydatin (PLD), a biological precursor of resveratrol, has antioxidant activity. A combination of PEA and PLD could, conceivably, have beneficial effects on oxidative stress produced by inflammatory processes. In the present study we investigated the effects of a co-micronized composite containing PEA and PLD (m(PEA/PLD)) in a model of testosterone-induced benign hyperplasia (BPH). BPH was provoked in rats by daily administration of testosterone propionate (3mg/kg) for 14days. This protocol leads to alterations in prostate morphology and increased levels of prostaglandin E2 and dihydrotestosterone as well as of 5α-reductase 1 and 5α-reductase 2 expression. Moreover, testosterone induced marked inflammation in terms of an increase in nuclear translocation of nuclear factor-κB p65 and consequently in IκB-α degradation as well as disregulation of inducible nitric oxide synthase, cyclooxygenase-2 and manganese superoxide dismutase expression and in the apoptosis pathway. Our results show, for the first time, that m(PEA/PLD) is capable of decreasing prostate weight and dihydrotestosterone production in BPH-induced rats. These effects were most likely correlated to the anti-inflammatory and apoptotic effects of m(PEA/PLD). Accordingly, these results support the view that m(PEA/PLD) should be further studied as a potent candidate for the management of BPH.

Keywords: Benign prostatic hyperplasia; Inflammation; Palmitoylethanolamide; Polydatin.

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
  • Amides
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Dihydrotestosterone / metabolism
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • Drug Combinations
  • Drug Compounding
  • Ethanolamines / chemistry
  • Ethanolamines / pharmacology*
  • Glucosides / chemistry
  • Glucosides / pharmacology*
  • Inflammation Mediators / metabolism
  • Male
  • Oxidative Stress / drug effects
  • Palmitic Acids / chemistry
  • Palmitic Acids / pharmacology*
  • Prostate / drug effects*
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Hyperplasia / chemically induced
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • Testosterone Propionate

Substances

  • Amides
  • Anti-Inflammatory Agents
  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Drug Combinations
  • Ethanolamines
  • Glucosides
  • Inflammation Mediators
  • Palmitic Acids
  • Stilbenes
  • Dihydrotestosterone
  • palmidrol
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • Dinoprostone
  • Testosterone Propionate
  • polydatin