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Thymoquinone mitigate ischemia-reperfusion-induced liver injury in rats: a pivotal role of nitric oxide signaling pathway.
Naunyn Schmiedebergs Arch Pharmacol. 2017 Jan; 390(1):69-76.NS

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt. elshimaa.arafa@pharm.bsu.edu.eg. Department of Pharmacology and Toxicology, College of Pharmacy and Health Sciences, Ajman University of Science and Technology, Ajman, United Arab Emirates. elshimaa.arafa@pharm.bsu.edu.eg.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafr El-Sheikh University, Kafr El-Sheikh, Egypt.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt. Department of Pharmacology, College of pharmacy, Al Jouf University, Al Jouf, Kingdom of Saudi Arabia.Department of Pharmacology, Faculty of Veterinary medicine, Beni-Suef University, Beni-Suef, 62514, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27717985

Citation

Abd-Elbaset, Mohamed, et al. "Thymoquinone Mitigate Ischemia-reperfusion-induced Liver Injury in Rats: a Pivotal Role of Nitric Oxide Signaling Pathway." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 390, no. 1, 2017, pp. 69-76.
Abd-Elbaset M, Arafa EA, El Sherbiny GA, et al. Thymoquinone mitigate ischemia-reperfusion-induced liver injury in rats: a pivotal role of nitric oxide signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 2017;390(1):69-76.
Abd-Elbaset, M., Arafa, E. A., El Sherbiny, G. A., Abdel-Bakky, M. S., & Elgendy, A. N. (2017). Thymoquinone mitigate ischemia-reperfusion-induced liver injury in rats: a pivotal role of nitric oxide signaling pathway. Naunyn-Schmiedeberg's Archives of Pharmacology, 390(1), 69-76. https://doi.org/10.1007/s00210-016-1306-7
Abd-Elbaset M, et al. Thymoquinone Mitigate Ischemia-reperfusion-induced Liver Injury in Rats: a Pivotal Role of Nitric Oxide Signaling Pathway. Naunyn Schmiedebergs Arch Pharmacol. 2017;390(1):69-76. PubMed PMID: 27717985.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thymoquinone mitigate ischemia-reperfusion-induced liver injury in rats: a pivotal role of nitric oxide signaling pathway. AU - Abd-Elbaset,Mohamed, AU - Arafa,El-Shaimaa A, AU - El Sherbiny,Gamal A, AU - Abdel-Bakky,Mohamed S, AU - Elgendy,Abdel Nasser A M, Y1 - 2016/10/07/ PY - 2016/06/27/received PY - 2016/09/23/accepted PY - 2016/10/9/pubmed PY - 2017/2/22/medline PY - 2016/10/9/entrez KW - Hepatic ischemia–reperfusion KW - NOSTRIN KW - Thymoquinone KW - eNOS KW - iNOS SP - 69 EP - 76 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 390 IS - 1 N2 - 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. SN - 1432-1912 UR - https://www.unboundmedicine.com/medline/citation/27717985/Thymoquinone_mitigate_ischemia_reperfusion_induced_liver_injury_in_rats:_a_pivotal_role_of_nitric_oxide_signaling_pathway_ L2 - https://dx.doi.org/10.1007/s00210-016-1306-7 DB - PRIME DP - Unbound Medicine ER -