Honokiol attenuates torsion/detorsion-induced testicular injury in rat testis by way of suppressing endoplasmic reticulum stress-related apoptosis

Urology. 2012 Apr;79(4):967.e5-11. doi: 10.1016/j.urology.2011.11.027. Epub 2012 Jan 27.

Abstract

Objective: To investigate the protective effect of honokiol, a phytochemical used in traditional medicine, on testicular injury after torsion/detorsion (T/D) in a rat model. Testicular torsion is a medical emergency that can cause impairment of semen quality and permanent testicular atrophy or loss.

Methods: Male Wistar rats were randomized to each time point of each group (n = 6/time point/group). After 2 hours of torsion, the testes were counter-rotated to the natural position. The rats in each group underwent a sham operation, T/D, or T/D with honokiol treatment (5 mg/kg and 10 mg/kg intraperitoneally, immediately before detorsion). Bilateral orchiectomy was performed at 6 and 24 hours and 3 months after detorsion. The testes were examined histologically. Apoptosis and endoplasmic reticulum stress were detected by Western blot.

Results: Histologic examination revealed that testicular T/D induced acute injury after 6 and 24 hours, and spermatogenesis was decreased at 3 months of follow-up. At 24 hours after T/D, increases were found in the activation of apoptosis-related molecules [poly (ADP-ribose) polymerase and caspases 3 and 7], and the expression levels of endoplasmic reticulum stress-associated molecules (phosphorylated-eukaryotic translation initiation factor 2 subunit α and CCAAT/enhancer-binding protein homologous protein). These increases were significantly reversed with honokiol treatment. Furthermore, honokiol effectively reversed the inhibition of spermatogenesis in testes treated with T/D for 3 months.

Conclusion: The results of our study have shown that the endoplasmic reticulum stress-related apoptotic pathway is involved in testicular injury after testicular T/D. It remains to be determined whether alterations in this pathway would have a protective affect against reperfusion damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Biphenyl Compounds / pharmacology*
  • Drugs, Chinese Herbal / pharmacology*
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / physiology*
  • Lignans / pharmacology*
  • Male
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / prevention & control
  • Spermatic Cord Torsion / physiopathology*
  • Spermatogenesis / physiology

Substances

  • Biphenyl Compounds
  • Drugs, Chinese Herbal
  • Lignans
  • honokiol