title: Thymoquinone mitigate ischemia-reperfusion-induced liver injury in rats: a pivotal role of nitric oxide signaling pathway.
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.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abd-Elbaset
authors.affiliation: 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.
authors.forename: El-Shaimaa A
authors.initials: EA
authors.lastname: Arafa
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafr El-Sheikh University, Kafr El-Sheikh, Egypt.
authors.forename: Gamal A
authors.initials: GA
authors.lastname: El Sherbiny
authors.affiliation: 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.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Abdel-Bakky
authors.affiliation: Department of Pharmacology, Faculty of Veterinary medicine, Beni-Suef University, Beni-Suef, 62514, Egypt.
authors.forename: Abdel Nasser A M
authors.initials: AN
authors.lastname: Elgendy
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D016227:Benzoquinones / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D016227:Benzoquinones; D015415:Biomarkers; D009569:Nitric Oxide; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C003466:thymoquinone; D000111:Acetylcysteine
keywords: Hepatic ischemia–reperfusion; NOSTRIN; Thymoquinone; eNOS; iNOS