Thymoquinone prevents endoplasmic reticulum stress and mitochondria-induced apoptosis in a rat model of partial hepatic warm ischemia reperfusion

Biomed Pharmacother. 2017 Oct:94:964-973. doi: 10.1016/j.biopha.2017.08.018. Epub 2017 Aug 12.

Abstract

This study was undertaken to evaluate the protective effect of thymoquinone (TQ), the bioactive compound of Nigella sativa seeds, against warm ischemia-reperfusion (I/R) injury in liver. Rats were given an oral administration of a vehicle solution (sham group) or TQ at the appropriate dose (10, 20, 30 and 40mg/kg) for ten days consecutively. Following, they were subjected to 60min of partial hepatic ischemia followed by 24h of reperfusion. .Transaminase activities, histopathological changes, TNFα and antioxidant parameters were evaluated. Also, endoplasmic reticulum (ER) stress, mitochondrial damage and apoptosis were studied. In addition, ERK and P38 phosphorylation was determined by Western blot technique. We found that TQ at 30mg/kg is the effective dose to protect rat liver against I/R injury. Moreover, 30mg/kg of TQ prevented histological damages, inflammation and oxidative stress. Interestingly, it decreased the expression of ER stress parameters including GRP78, CHOP and caspase-12. In parallel, it improved mitochondrial function and attenuated the expression of apoptotic parameters. Furthermore, TQ significantly enhanced ERK and P38 phosphorylation. In conclusion, we demonstrated the potential of TQ to protect the rat liver against I/R injury through the prevention of ER stress and mitochondrial dysfunction. These effects implicate the prevention of oxidative stress.

Keywords: Apoptosis; Endoplasmic reticulum stress; Ischemia reperfusion injury; Oxidative stress; Thymoquinone.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis / drug effects*
  • Benzoquinones / pharmacology*
  • Endoplasmic Reticulum Stress / drug effects*
  • Ischemia / drug therapy*
  • Ischemia / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • Phosphorylation / drug effects
  • Protective Agents / pharmacology
  • Rats
  • Rats, Wistar
  • Reperfusion / methods
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Warm Ischemia / methods
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antioxidants
  • Benzoquinones
  • Protective Agents
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases
  • thymoquinone