Tert-Butylhydroquinone Protects Liver Against Ischemia/Reperfusion Injury in Rats Through Nrf2-Activating Anti-Oxidative Activity

Transplant Proc. 2017 Mar;49(2):366-372. doi: 10.1016/j.transproceed.2016.12.008.

Abstract

Background: Hepatic ischemia/reperfusion (I/R) injury is a serious complication that occurs in surgical operations such as hepatectomy and liver transplantation. NF-E2-related factor 2 (Nrf2) is a transcription factor that has been proven against inflammatory and oxidative injury. Tert-butylhydroquinone (tBHQ), a widely used Nrf2 activator, is a common food preservative. In this study, we attempt to investigate the potential protective role of tBHQ in hepatic I/R injury.

Methods: Twenty adult male rats were randomly divided into four groups: (1) sham+vehicle group; (2) I/R+vehicle group; (3) sham+tBHQ group; and (4) I/R+tBHQ group. The vehicle or tBHQ was divided into three injections at intervals of 12 hours in a model of hepatic I/R injury. Fluorescence quantitative polymerase chain reaction and Western blot analysis were used to examine Nrf2 mRNA and protein expression. The concentrations of malondialdehyde and superoxide dismutase activity were accessed, respectively.

Results: Compared with the sham+vehicle group, Nrf2 expression, malondialdehyde, content and serum alanine aminotransferase were significantly increased in the I/R+vehicle group, whereas superoxide dismutase activity was significantly decreased. However, in the I/R+tBHQ group, tBHQ ameliorated tissue damage; promoted glutathione-S-transferase, quinine oxidoreductase 1, and glutamate cysteine ligase inductions; and regained redox homeostasis in comparison with the I/R+vehicle group. Furthermore, the present study indicated that preconditioning with tBHQ suppressed the I/R-induced increase in the apoptotic protein levels of caspase-3, as well as the I/R-induced decrease in the levels of anti-apoptotic protein bcl-2.

Conclusions: t-BHQ exerted potent anti-inflammatory effects in I/R-induced liver injury, and tBHQ would be a new effectively therapeutic measure for preventing hepatic I/R injury during liver surgery.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Glutathione Transferase / metabolism
  • Hydroquinones / pharmacology*
  • Liver / metabolism
  • Male
  • Malondialdehyde / metabolism
  • NF-E2-Related Factor 2 / drug effects*
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*

Substances

  • Antioxidants
  • Hydroquinones
  • NF-E2-Related Factor 2
  • Protective Agents
  • RNA, Messenger
  • Malondialdehyde
  • 2-tert-butylhydroquinone
  • Glutathione Transferase
  • Caspase 3