Antioxidant mitoquinone suppresses benign prostatic hyperplasia by regulating the AR-NLRP3 pathway

Redox Biol. 2023 Sep:65:102816. doi: 10.1016/j.redox.2023.102816. Epub 2023 Jul 11.

Abstract

Mitoquinone (MitoQ), a mitochondria-targeted antioxidant, has been used to treat several diseases. The present study aimed to investigate the therapeutic effects of MitoQ in benign prostatic hyperplasia (BPH) models and their underlying molecular mechanisms. In this study, we determined that MitoQ inhibited dihydrotestosterone (DHT)-induced cell proliferation and mitochondrial ROS by inhibiting androgen receptor (AR) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling in prostate epithelial cells. Molecular modeling revealed that DHT may combine with AR and NLRP3, and that MitoQ inhibits both AR and NLRP3. AR and NLRP3 downregulation using siRNA showed the linkage among AR, NLRP3, and MitoQ. MitoQ administration alleviated pathological prostate enlargement and exerted anti-proliferative and antioxidant effects by suppressing the AR and NLRP3 signaling pathways in rats with BPH. Hence, our findings demonstrated that MitoQ is an inhibitor of NLPR3 and AR and a therapeutic agent for BPH treatment.

Keywords: Androgen receptor; Benign prostatic hyperplasia; Dihydrotestosterone; Mitoquinone; NLRP3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Humans
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • Prostatic Hyperplasia* / chemically induced
  • Prostatic Hyperplasia* / drug therapy
  • Prostatic Hyperplasia* / genetics
  • Rats
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism

Substances

  • Antioxidants
  • mitoquinone
  • Receptors, Androgen
  • NLR Family, Pyrin Domain-Containing 3 Protein