Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Ischemia-reperfusion (I/R) injury is a pathological process which magnifies with the ensuing inflammatory response and endures with the increase of oxidants especially during reperfusion. The present study was conducted to assess the possible modulatory effects of two biologically active constituents of plant origin named apigenin and plumbagin, where the former is the active constituent extracted from the roots of traditional medicinal plant Plumbago zeylanica L and the latter is a flavonoid that exists abundantly in numerous herbs and vegetables, including chamomile, thyme, parsley and broccoli., on the dire role of high mobility group box (HMGB1) as well as the associated inflammation, oxidative stress and apoptotic cell death following hepatic I/R. Six groups of rats were included: sham operated, sham operated treated with apigenin, sham operated treated with plumbagin, I/R (30 min ischemia and 1 h reperfusion) , I/R treated with apigenin and I/R treated with plumbagin. Pretreatment with apigenin and plumbagin markedly improved hepatic function and histology, as indicated by reduced transaminase levels, lactate dehydrogenase activity and ameliorated tissue pathological changes. They significantly reduced high mobility group box 1 (HMGB1) expression and subsequently suppressed inflammatory cascades, as liver NF-mB and TNF-Ü as well as MPO activity. Both were capable of interrupting ROS-HMGB1loop as evident by restored liver GSH, decreased liver lipoperoxidation, and enhanced glutathione peroxidase (GPx) activity. Simultaneously, apoptosis was significantly ameliorated by increasing the Bcl-2/Bax ratio

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