Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 390, Issue 1, pp 69–76 | Cite as

Thymoquinone mitigate ischemia-reperfusion-induced liver injury in rats: a pivotal role of nitric oxide signaling pathway

  • Mohamed Abd-Elbaset
  • El-Shaimaa A. ArafaEmail author
  • Gamal A. El Sherbiny
  • Mohamed S. Abdel-Bakky
  • Abdel Nasser A.M. Elgendy
Original Article


Oxidative and nitrosative stress-induced endothelial cell damage play an essential role in the pathogenesis of hepatic ischemia-reperfusion (IR) injury. IR is associated with reduced eNOS expression and exacerbated by superimposed stress. NOSTRIN induces intracellular endothelial nitric oxide synthase (eNOS) translocation and inducible nitric oxide synthase (iNOS) increases nitric oxide (NO) production. Our aim was to assess hepatic expression of iNOS, eNOS, and NOSTRIN in IR with or without N-acetylcysteine (NAC) or thymoquinone (TQ) pretreatment and to compare their hepatoprotective effects. Surgical induction of IR was performed by occlusion of hepatic pedicle for 30 min with mini-clamp and reperfused for 30 min. The effects of TQ (20 mg/kg/day) or NAC (300 mg/kg/day) administered orally for 10 days were evaluated by serum ALT and AST, oxidative stress parameters, NO production, and histopathological analysis. Also, localization and expression of iNOS, eNOS, and NOSTRIN were assessed by immunofluorescence. TQ or NAC pretreatment significantly decreased elevated serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and myeloperoxidase (MPO) activities, malondialdehyde (MDA) level, and NO production. In addition, they restored the depleted GSH content and alleviated histopathological changes. Furthermore, they up-regulated eNOS and down-regulated iNOS and NOSTRIN expressions. TQ exerts its hepatoprotective effect, at least in part, by nitric oxide signaling pathway through modulation of iNOS, eNOS, and NOSTRIN expressions as well as suppression of oxidative stress.


Thymoquinone Hepatic ischemia–reperfusion iNOS eNOS NOSTRIN 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Mohamed Abd-Elbaset
    • 1
  • El-Shaimaa A. Arafa
    • 1
    • 2
    Email author
  • Gamal A. El Sherbiny
    • 3
  • Mohamed S. Abdel-Bakky
    • 4
    • 5
  • Abdel Nasser A.M. Elgendy
    • 6
  1. 1.Department of Pharmacology and Toxicology, Faculty of PharmacyBeni-Suef UniversityBeni-SuefEgypt
  2. 2.Department of Pharmacology and Toxicology, College of Pharmacy and Health SciencesAjman University of Science and TechnologyAjmanUnited Arab Emirates
  3. 3.Department of Pharmacology and Toxicology, Faculty of PharmacyKafr El-Sheikh UniversityKafr El-SheikhEgypt
  4. 4.Department of Pharmacology and Toxicology, Faculty of PharmacyAl-Azhar UniversityCairoEgypt
  5. 5.Department of Pharmacology, College of pharmacyAl Jouf UniversityAl JoufKingdom of Saudi Arabia
  6. 6.Department of Pharmacology, Faculty of Veterinary medicineBeni-Suef UniversityBeni-SuefEgypt

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