Paeonol protects against testicular ischaemia-reperfusion injury in rats through inhibition of oxidative stress and inflammation

Andrologia. 2020 Jul;52(6):e13599. doi: 10.1111/and.13599. Epub 2020 Apr 21.

Abstract

Ischaemia-reperfusion (IR) is the most common form of testicular injury that results in oxidative damage and inflammation ending by subinfertility. Paeonol, a natural phenolic compound, exhibits antioxidant and anti-inflammatory effects. Thus, the present study investigated the role of paeonol in rat testicular IR injury. Thirty adult Wistar rats were randomly divided into five groups; sham, sham treated with paeonol, IR injury, and IR pre-treated with paeonol at low and high doses. Serum testosterone and testicular levels of malondialdehyde and reduced glutathione (GSH) besides superoxide dismutase (SOD) activity were determined. Gene quantifications for tumour necrosis factor-α (TNF-α), hypoxia-inducible factor-1α (HIF-1α) and heat shock protein 70 (HSP70) were also assessed. Histopathological pictures and the immunohistochemical expression of testicular nuclear factor erythroid 2-related factor 2 (Nrf2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were shown. Pre-treatment with paeonol prevented the drop in serum testosterone, alongside with improvement of testicular malondialdehyde and GSH levels plus SOD activity. Paeonol regained the normal spermatogenesis with prevention of IR-induced increase in TNF-α, HIF-1α and HSP70 gene expression besides IL-1β and IL-6 immunostaining and reduction in Nrf2 protein expression. Paeonol exerted a dose-dependent beneficial effect on testicular IR injury. This effect was achieved by its antioxidant and anti-inflammatory effects.

Keywords: HIF-1α; HSP70; Nrf2; TNF-α; paeonol; testicular ischaemia-reperfusion.

MeSH terms

  • Acetophenones / pharmacology*
  • Animals
  • Gene Expression / drug effects
  • Glutathione / drug effects
  • Glutathione / metabolism
  • HSP70 Heat-Shock Proteins / drug effects
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / drug effects
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunohistochemistry
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Malondialdehyde / metabolism
  • NF-E2-Related Factor 2 / drug effects
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Spermatic Cord Torsion / metabolism*
  • Spermatic Cord Torsion / pathology
  • Superoxide Dismutase / drug effects
  • Superoxide Dismutase / metabolism
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / pathology
  • Testosterone / metabolism
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Acetophenones
  • HSP70 Heat-Shock Proteins
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • IL1B protein, rat
  • Il6 protein, rat
  • Interleukin-1beta
  • Interleukin-6
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Tumor Necrosis Factor-alpha
  • paeonol
  • Testosterone
  • Malondialdehyde
  • Superoxide Dismutase
  • Glutathione