Zafirlukast protects against hepatic ischemia-reperfusion injury in rats via modulating Bcl-2/Bax and NF-κB/SMAD-4 pathways.

Autor: Mahmoud HM; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt. Electronic address: heba.taha@pharm.bsu.edu.eg., Elsayed Abouzed DE; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Sohag University, Sohag, 82524, Egypt. Electronic address: deiaaabozed@pharm.sohag.edu.eg., Abo-Youssef AM; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt. Electronic address: amira.aboyoussef@gmail.com., Hemeida RAM; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Deraya University, Minya, 61519, Egypt. Electronic address: Ramadan.hemeida@deraya.edu.eg.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2023 Sep; Vol. 122, pp. 110498. Date of Electronic Publication: 2023 Jul 05.
DOI: 10.1016/j.intimp.2023.110498
Abstrakt: Hepatic ischemia/reperfusion injury (IRI) is a clinical problem commonly during liver transplantation and other liver surgery. This study aimed to evaluate the protective effect of zafirlukast (ZFK) on IR-induced hepatic injury and investigate its relevant protective mechanism. Thirty-two male Wistar albino rats were randomly allocated to four groups: sham, IRI, ZFK, and ZFK + IR groups. ZFK was administered orally in a dose of 80 mg/kg/day for 10 consecutive days. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) levels, and gamma glutamyl transferase (GGT) activity were estimated. Liver tissues were used to assess oxidative stress biomarkers including malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NOx), and reduced glutathione (GSH) contents. Inflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-33 (IL-33), in addition to apoptosis biomarkers, BCL2 associated X protein (Bax), B-cell lymphoma 2 (Bcl2) and galactine-9 (GAL9) proteins were also assessed. Western blot analysis was performed for vascular endothelial growth factor (VEGF) and fibrinogen expressions. Immunohistochemical analysis for hepatic nuclear factor-kappa B (NF-κB) and SMAD-4 was done in addition to histopathological examination. Our study revealed that ZFK pre-treatment resulted in liver function restoration and oxidative stress correction. Moreover, inflammatory cytokines were significantly reduced and a remarkable reduction of apoptosis, angiogenesis, and clotting formation has been indicated. Additionally, a significant reduction in SMAD-4 and NF-kB protein expressions was observed. These results were supported by hepatic architecture improvement. Our findings revealed that ZFK possesses a potential protective effect against liver IR possibly through its antioxidant, anti-inflammatory and anti-apoptotic properties.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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