title: The potential curative effect of rebamipide in hepatic ischemia/reperfusion injury.
abstract: Rebamipide (Reba), a gastroprotective drug, has signified its hepatoprotective activity; however, its possible post-therapeutic intervention in hepatic ischemia/reperfusion (I/R) remains elusive. Consequently, the intent of this study was to test Reba modulatory effect on nuclear factor (NF)-κB signaling in hepatic I/R model. Rats were randomized into sham, I/R, Reba 60, and Reba100 (60 and 100 mg/kg, respectively) groups. Ischemia was induced for 30 min followed by 3-day reperfusion to set up a model of partial (70%) warm hepatic ischemia. Post-treatment with Reba reduced the serum level of alanine transaminase, improved histopathological alterations of the liver, and elevated hepatic adenosine triphosphate. It also lowered hepatic lipid peroxides and increased both total antioxidant capacity and nitric oxide. Besides, Reba decreased tumor necrosis factor-α, interferon-γ, intercellular adhesion molecule-1, myeloperoxidase, prostaglandin E2, cyclooxygenase-2 expression/content, and caspase-3 activity. Reba also upregulated the gene expression/content of sirtuin 1 (SIRT-1), while it downregulated that of high mobility group box (HMGB)1 and reduced the expression/content of NF-κB p65/pS536-NF-κB and the content of pT180/Y182-p38MAPK. Reba provided tenable hepato-therapeutic mechanisms to mitigate events concomitant with hepatic I/R via inhibition of NF-κB p65 and modulation of its influential signals (SIRT-1, HMGB1, p38MAPK) associated with its antiinflammatory, antioxidant, and antiapoptotic impacts.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty Pharmacy, October 6 University, Giza, 12585, Egypt.
authors.forename: Abdallah M
authors.initials: AM
authors.lastname: Gendy
authors.affiliation: Department of Pharmacology and Toxicology, Faculty Pharmacy, Cairo University, Kasr El-Aini Str, Cairo, 11562, Egypt. dalaal.abdallah@pharma.cu.edu.eg.
authors.forename: Dalaal M
authors.initials: DM
authors.lastname: Abdallah
authors.affiliation: Department of Pharmacology and Toxicology, Faculty Pharmacy, Cairo University, Kasr El-Aini Str, Cairo, 11562, Egypt.
authors.forename: Hanan S
authors.initials: HS
authors.lastname: El-Abhar
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D015363:Quinolones / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056564:Sirtuin 1 / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D015363:Quinolones; D051996:Transcription Factor RelA; D048051:p38 Mitogen-Activated Protein Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; C052785:rebamipide; D000409:Alanine
keywords: HMGB1; Hepatic ischemia/reperfusion; NF-κB; Rebamipide; Sirtuin1; p38 MAPK