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040 _aEG-GiCUC
_beng
_cEG-GiCUC
041 0 _aeng
049 _aDeposite
097 _aPh.D
099 _aCai01.08.09.Ph.D.2021.Ma.P
100 0 _aMai Elsayed Elsaid Ghoneim
245 1 4 _aThe potential effect of artesunate in hepatic ischemia reperfusion model in rats /
_cMai Elsayed Elsaid Ghoneim ; Supervised Dalaal Moustafa Abdallah , Hanan Salah Edin Elabhar
246 1 5 _aالتأثير الممكن للأرتيسونات في نموذج الفقر الدموى للكبد ثم إعادة التروية فى الجرذان
260 _aCairo :
_bMai Elsayed Elsaid Ghoneim ,
_c2021
300 _a147 P. :
_bcharts , facsimiles ;
_c25cm
502 _aThesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology
520 _aThe antimalarial drug artesunate (Art) has proven its beneficial effects against ischemia/reperfusion (I/R) injury in diverse organs, but its potential role against hepatic I/R is still obscure. This study, hence, examined whether treatment with Art alone or in combination with rapamycin (Rapa), an mTOR inhibitor, can ameliorate hepatic I/R injury via targeting the NLRP3 inflammasome signaling pathway.Rats were divided into hepatic sham- and I/R-operated rats.The latter were either left untreated (I/R group) or treated with Art, Rapa, or their combination.On the molecular level, all treatment regimens succeeded to hinder inflammasome assembly and activation, assessed as NLRP3, ASC cleaved caspase-1, caspase-11, N-terminal cleaved gasdermin-D (GSDMD-N), IL-1Ý, and IL-18. This effect was associated by the inhibition in the harmful signaling pathways HMGB1/RAGE and TLR4/MyD88/TRAF6 to inactivate the transcription factor NF-mB and the production of its pro-inflammatory cytokines IL-1Ý, IL-18, IL-6, and TNF-Ü. Additionally, this effect entailed the inhibition of ICAM-1/MPO/ROS cascade, which in turn hampered cell demise induced by apoptosis, manifested as correction of the imbalanced Bcl2/Bax, as well as pyroptosis (LDH, cleaved caspase-1, caspase-11, GSDMD-N, IL-1Ý, IL-18), and necrosis.The corrected pathways were reflected on the improved liver function (serum ALT, AST, and LDH) and microscopical hepatic architecture. Noteworthy, the effect of Art on all parameters exceeded significantly that of Rapa and even improved the effect of the latter in the combination group. In conclusion, our results suggest novel roles for Art in abating functional and structural I/R-induced hepatic abnormalities via several traversing cross-talking pathways that succeeded to abate NLRP3 inflammasome and cell death
530 _aIssued also as CD
653 4 _aNLRP3
653 4 _aOxidative stress
653 4 _aTLR4
700 0 _aDalaal Moustafa Abdallah ,
_eSupervisor
700 0 _aHanan Salah Edin Elabhar,
_eSupervisor
856 _uhttp://172.23.153.220/th.pdf
905 _aNazla
_eRevisor
905 _aShimaa
_eCataloger
942 _2ddc
_cTH
999 _c81850
_d81850