Thesis (Ph.D.) – Cairo University. Faculty of Pharmacy. Department of Pharmacology & Toxicology.

Includes bibliographical references.

Rebamipide (Reba), a gastroprotective drug, has signified its hepatoprotective activity; however, its possible 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 two sets. Each set contains sham, I/R, Reba 60, and Reba100 (60 & 100 mg/kg, respectively) groups. Ischemia was induced for 30 min followed by one and 3-day reperfusion for prophylactic and curative set, respectively to set up a model of partial (70%) warm hepatic ischemia. Reba administration reduced the serum level of alanine transaminase, improved histopathological alterations of the liver, and elevated hepatic adenosine triphosphate. It also lowered hepatic lipid peroxides, increased its total antioxidant capacity, and nitric oxide. Besides, Reba decreased tumor necrosis factor-α, interferon-γ, intercellular adhesion molecule-1, myeloperoxidase, prostaglandin E2, cyclo-oxygenase-2 expression/content, and caspase-3 activity. Reba also upregulated the gene expression/content of sirtuin (SIRT)-1, while it downregulated that of high mobility group box (HMGB)1 and reduced the expression/content of NF-κB p65 and 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 anti-inflammatory, anti-oxidant, and anti-apoptotic impacts.

Text in English, abstracts in English and Arabic.