000			03169cam a2200337 a 4500
003			EG-GiCUC
005			20250223032029.0
008			180809s2018 ua do f m 000 0 eng d
040			_aEG-GiCUC _beng _cEG-GiCUC
041	0		_aeng
049			_aDeposite
097			_aPh.D
099			_aCai01.08.09.Ph.D.2018.Sa.P
100	0		_aSarah Ahmed Abdelaal Ahmed
245	1	4	_aThe potential modulatory effect of an inhibitor of HMG-CoA reductase enzyme on hippocampal neuronal damage induced by transient global cerebral ischemia in rats / _cSarah Ahmed Abdelaal Ahmed ; Supervised Hanan Salah Eldin Elabhar , Mai Ahmed Galal
246	1	5	_aفى تلف خلايا قرن آمون العصبية الناتج عن إحتباس الدم الشامل المؤقت فى مخ الجرذان (HMG-CoA reductase) التأثير المعدل المحتمل لأحد مثبطى نشاط إنزيم
260			_aCairo : _bSarah Ahmed Abdelaal Ahmed , _c2018
300			_a200 P. : _bcharts , photographs ; _c25cm
502			_aThesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology
520			_aStatins were reported to lower the CoQ10 content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg), CoQ10 (10mg/kg) and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of MDA, NO and boosted GSH and SOD. They also opposed the up-regulation of gp91phox, and p47phox subunits of NADPH oxidase. Meanwhile, both agents reduced content/expression of TNF-Ü, iNOS, NF-mBp65, ICAM-1 and MPO. Besides, all regimens abated cytochrome C, caspase-3 and Bax, but increased Bcl-2 in favor of cell survival. On the molecular level, they increased p-Akt and its downstream target p-FOXO3A, with the inhibition of the nuclear content of FOXO3A to downregulate the expression of Bim, a pro-apoptotic gene. Additionally, both treatments downregulate the JNK3/c-Jun signaling pathway. The effect of the combination regimen overrides that of either treatment alone. These effects were reflected on the alleviation of the hippocampal damage in CA1 region inflicted by I/R. Together, these findings accentuate the neuroprotective potentials of both treatments against global I/R by virtue of their rigorous multi-pronged actions, including suppression of hippocampal oxidative stress, inflammation, and apoptosis with the involvement of the Akt/FOXO3A/Bim and JNK3/c-Jun/Bax signaling pathways. The study also nominates CoQ10 as an adds-on therapy with statins
530			_aIssued also as CD
653		4	_aCA1
653		4	_aCaspase-3
653		4	_aMPO
700	0		_aHanan Salah Eldin Elabhar , _eSupervisor
700	0		_aMai Ahmed Galal , _eSupervisor
856			_uhttp://172.23.153.220/th.pdf
905			_aNazla _eRevisor
905			_aSamia _eCataloger
942			_2ddc _cTH
999			_c67004 _d67004