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003			OSt
005			20250223033348.0
008			241218s2023 |||a|||f m||| 000 0 eng d
040			_aEG-GICUC _beng _cEG-GICUC _dEG-GICUC _erda
041	0		_aeng _beng _bara
049			_aDeposit
082	0	4	_a615.1
092			_a615.1 _221
097			_aM.Sc
099			_aCai01.08.09.M.Sc.2023.Ma.S
100	0		_a Mai Abdelhalim Mohamed Abdelhalim, _epreparation.
245	1	0	_aStudy of the possible therapeutic effect of LCZ696 in chemotherapy induced pulmonary fibrosis in rats / _cby Mai Abdelhalim Mohamed Abdelhalim ; the Supervision of Dr. Dalaal Moustafa Abdallah, Dr. Noha Nagah Nassar, Dr. Gehan Sobhy Georgy.
246	1	5	_a/ فى التليف الرئوى الناتج عن العلاج الكيميائى فى الجرذان LCZ696دراسة التأثير العلاجي المحتمل ل
264		0	_c2023.
300			_a176 pages : _billustrations ; _c25 cm. + _eCD.
336			_atext _2rda content
337			_aUnmediated _2rdamedia
338			_avolume _2rdacarrier
502			_aThesis (M.Sc.)-Cairo University, 2023.
504			_aBibliography: pages 143-176.
520			_aIntroduction: Pulmonary fibrosis (PF) is a progressively devastating lung disease with no definitive therapeutic strategy. Several factors may precipitate PF including chemotherapy, environmental agents, and infection (as Coronavirus). Disruption of the lung oxidant/antioxidant status along with increased activation of inflammatory and apoptotic mediators are considered as major findings implicated in PF pathogenesis. This study investigated the prospect therapeutic effect of valsartan alone or combined with sacubitril (LCZ696) in chemotherapy-induced PF. Methods: Rats were randomly allocated into four groups; normal control, methotrexate (MTX)-induced PF (once weekly for 2 consecutive weeks), MTX-induced PF treated with valsartan or LCZ696 administered for 28 days initiated 2 weeks after PF induction. Lung histopathological examinations (H&E and Masson’s trichome) and immunohistochemical determination of α-smooth muscle actin (α-SMA) were performed. Additionally, pro-fibrotic, inflammatory, apoptotic, and oxidative stress biomarkers were assayed in lung tissues. Results: LCZ696 exhibited inhibition of the pro-fibrotic biomarker transforming growth factor-1β (TGF-1β) along with Smad7 increment with marked suppression of caspase-3, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) compared to valsartan. Though valsartan showed partial improvement, LCZ696 normalized α-SMA and oxidative/nitroactive stress biomarkers (catalase and nitric oxide). Furthermore, histopathological examination of LCZ696 treated group considerably inhibited inflammation and fibrosis in addition to remarkable reduction of collagen deposition. Conclusion and discussion: Collectively, the combined therapy LCZ696 showed superior effects to single valsartan regimen and may be considered as a promising therapeutic modality for chemotherapy-induced PF.
520			_aتم تصميم الدراسة الحالية بهدف أساسي لتوضيح الإمكانية العلاجية لمثبط مستقبلات الأنجيوتنسين وكابح النيبريليسين الأول في فئته (ساكيوبتريل/فالسارتان) كنظام علاجي مشترك مقارنة بالعلاج الفردي فالسارتان في نموذج تليف الرئة الناجم عن الميثوتريكسيت. الدراسة تهدف إلى تمييز الآليات الجزيئية المعقدة واستقصاء تأثيراتها على الأحداث الرئيسية مثل الإجهاد التأكسدي، والالتهاب، والموت المبرمج، والتليف. علاوةً على ذلك، توسع الاستفسار ليشمل استكشاف مسار Neprilysin/Natriuretic peptides/ TGF-β1/Smad3 من أجل تحقيق هذه الأهداف، خضعت الدراسة الحالية لتقسيم إلى مرحلتين: المرحلة التجريبية والمرحلة الأساسية. تمت المرحلة التجريبية لتحديد الجرعة الفعّالة المثلى للنظام العلاجي المشترك ساكيوبيتريل/فالسارتان.
530			_aIssues also as CD.
546			_aText in English and abstract in Arabic & English.
650		7	_aDurgs _2qrmak
653		0	_aα-SMA _aLCZ696 _apulmonary fibrosis, _aTGF-1β
700	0		_aDalaal Moustafa Abdallah _ethesis advisor.
700	0		_aNoha Nagah Nassar _ethesis advisor.
700	0		_aGehan Sobhy Georgy _ethesis advisor.
900			_b01-01-2023 _cDalaal Moustafa Abdallah _cNoha Nagah Nassar _cGehan Sobhy Georgy _UCairo University _FFaculty of Pharmacy _DDepartment of Pharmacology & Toxicology
905			_aShimaa _eHuda
942			_2ddc _cTH _e21 _n0
999			_c169553